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Biomedical subjects

H Yang

Publications and source records attributed to H Yang.

At least 541 records · Page 30Linked to original sources
PubMed1998

Mutations in hepatitis B DNA polymerase associated with resistance to lamivudine do not confer resistance to adefovir in vitro.

To determine whether adefovir is active against lamivudine-resistant hepatitis B virus (HBV), the inhibition constants of adefovir diphosphate and lamivudine triphosphate for wild-type and mutant human HBV DNA polymerases, which contain amino acid substitutions associated with lamivudine resistance, were compared. Recombinant wild-type and mutant human HBV DNA polymerases were expressed and substantially purified using a baculovirus expression system and immunoaffinity chromatography. HBV DNA polymerase mutants M552I, M552V, and L528M/M552V showed resistance to lamivudine triphosphate with inhibition constants (Ki) increased by 8.0-fold, 19.6-fold, and 25.2-fold compared with that of wild-type HBV DNA polymerase. However, these mutants remained sensitive to adefovir diphosphate with the inhibition constants increasing by 1.3-fold and 2.2-fold or decreasing by 0.79-fold. The L528M single mutation, identified in patients with increasing HBV DNA levels during therapy with famciclovir, also remained sensitive to adefovir diphosphate with the inhibition constant increased by only 2.3-fold.

Adenine↗
PubMed1998

ETA receptor mediated inhibition of intracellular pH regulation in cultured bovine corneal epithelial cells.

The contributions were determined in primary cultures of bovine corneal epithelial cells (BCEC) of Na:H exchange (NHE) and vacuolar H+-ATPase (i.e. V-type) activity to the regulation of intracellular pH (pHi). Furthermore, we characterized the effects on pHi regulation of exposure to 1 microM ET-1 under control and acid loaded conditions. With the pH sensitive dye, 2',7' Bis (carboxyethyl)-5,6-carboxyfluorescein acetoxymethyl ester (BCECF-AM), the control pHi was 7.1 in NaCl (nominally HCO3-free) Ringers. Inhibition of NHE with 100 microM dimethylamiloride (DMA) rapidly decreased pHi by 0.37 units. Similarly, selective inhibition of V-type H+-ATPase with 10 microM bafilomycin A1 decreased pHi by 0.22 units. Following acid loading in NaCl Ringers with a 20 mm NH4Cl prepulse, pHi recovery was partially inhibited by exposure to either Na-free (NMGCl) Ringers, 100 microM DMA or 20 microM bafilomycin A1. Based on decreases in H+ efflux resulting from selective inhibition of NHE and V-type H+ pump activity, NHE activity accounts for 76% of the pHi recovery following acid loading. Under control conditions, ET-1 (1 microM) had no effect on pHi whereas ET-1 completely suppressed pHi recovery following acid loading in NaCl or NMGCl Ringers. This inhibitory effect was largely due to stimulation of ETA because in the presence of BQ-123 (10 microM), a selective ETA receptor antagonist, pHi recovery was completely restored. Suppression of pHi recovery also occurred following stimulation of protein kinase C (PKC) with 10(-7) m phorbol myristate (PMA) whereas 10(-7) m 4 alpha phorbol 12,13 didecanoate (PDD) had no effect. ET-1 failed to suppress pHi recovery after inhibition of PKC with 0.5 microM calphostin C suggesting that the inhibition of pHi recovery by ET-1 is a consequence of PKC stimulation. Similarly, inhibition of Ca2+-dependent calmodulin stimulated CaM II kinase with KN-62 (10 microM) reversed the suppression of pHi recovery by ET-1. Preinhibition of either protein phosphatase (PP), PP-1, PP-2A or PP-2B activity with 1 microM phenylarsine oxide, 10 nm okadaic acid, 10 microM cyclosporin A1 or 20 microM BAPTA, also obviated the suppression of pHi recovery by ET-1. Therefore ETA receptor mediated inhibition of pHi regulation following acid loading could be a consequence of either PKC or CaMII kinase stimulation. Each one of these kinases may in turn phosphorylate and thereby stimulate the activities of PP-1, PP-2A or PP-2B. An increase in the activity of any one of these protein phosphatases could lead to dephosphorylation of the NHE and V-type H+ pump. This alteration may prevent them from becoming adequately stimulated to elicit pHi recovery in response to acid loading.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

GLUT-4 Deficiency and severe peripheral resistance to insulin in the teleost fish tilapia.

Teleost fish, in general, are glucose intolerant; this trait has been attributed to piscine islets secreting insulin primary in response to amino acid secretogogues rather than glucose. However, pancreatic islet from the teleost fish tilapia, when transplanted into diabetic nude mice, were glucose responsive even though tilapia were severely glucose intolerant. This suggested a strong peripheral resistance to the glucostatic effects of insulin. Using Western blotting with polyclonal antibodies as well as Northern analysis for mRNA, tilapia tissues were found to be devoid of GLUT-4, the insulin-sensitive glucose transporter responsible for the hypoglycemic effect of insulin in mammals. The absence of GLUT-4 in peripheral tissues may explain why tilapia, and possibly other teleost fish, are severely glucose intolerant. This suggests that tilapia islets have evolved along mammalian lines to be glucose sensitive while tilapia peripheral tissue have diverged widely. Using the same methods, tilapia were found to have a very limited tissue distribution of the insulin-independent glucose transporter, GLUT-1, which is responsible for basal glucose transport in mammalian cells. It is suggested that tilapia provide a naturally occurring GLUT-4 knockout model.

Adipose Tissue↗
PubMed1998

Cervical uncinate process: an anatomic study for anterior decompression of the cervical spine.

Morphometric evaluation of 54 dry cervical spines from C3 to C7 (a total of 270 cervical vertebrae) was performed to determine the bony boundaries of the uncinate process for resection of the uncinate process for access to posterolateral osteophytes or herniated disks at the time of anterior cervical diskectomy. The uncinate processes were significantly higher (p < 0.01) at the C4-C6 levels (5.8 +/- 1.1 mm to 6.1 +/- 1.3 mm) than at the C3 or C7 levels. The distance between the medial and lateral margins of the base of the uncinate process was significantly smaller (p < 0.01) at the C3 level (4.9 +/- 0.7 mm) than at the C7 level (6.3 +/- 0.7 mm). The anteroposterior diameter of the medial margin of the uncinate process decreased gradually from the C5 (12.5 +/- 1.5 mm) to C7 levels (11.6 +/- 1.3 mm) (p < 0.05). The inter-uncinate distance widened from the C3 (19.2 +/- 1.5 mm) to the C7 (24.6 +/- 2.1 mm) levels (p < 0.01). The mid-anteroposterior diameter of vertebral body increased gradually from the C3 (14.7 +/- 1.1 mm) to the C7 levels (16.1 +/- 1.5 mm) (p < 0.01). The width of the vertebra increased gradually from C3 to C7 (from 19.2 +/- 1.8 mm at C3 to 25.6 +/- 2.0 mm at C7) (p < 0.01). Knowledge of all the aforementioned data may be helpful during anterolateral cervical uncosectomy or uncoforaminotomy.

Cadaver↗
PubMed1998

Clinical study on chronopharmacokinetics of digoxin in patients with congestive heart failure.

Fluorescence polarization immunoassay was used to study the chronopharmacokinetics of digoxin in 10 patients with congestive heart failure (CHF) who also served as self-controls. Our results showed that the serum digoxin concentration reached peak value 1 h after taking digoxin at 7:00 a.m., but the serum digoxin concentration reached the peak value 2 h after taking digoxin at 4:00 p.m. The average serum digoxin concentration area under curve was greater and the best maintainable time of serum concentration within 24 h after taking digoxin at 4 p.m. longer than those at 7:00 a.m. The heart rates were obviously lower and the cardiac function was significantly improved in 4:00 p.m. group.

Adult↗
PubMed1998

Patients with aortic stenosis: cardiac complications in non-cardiac surgery.

PURPOSE: To reassess the risk of patients with aortic stenosis (AS) undergoing non-cardiac surgery. METHODS: Following institutional approval, a retrospective chart audit of all patients with AS who underwent non-cardiac surgery in Hamilton between 1992 and 1994 was performed. For each AS case, a matching control was randomly selected. Data pertaining to pre-operative cardiac risk factors, intra-operative, and post-operative management were recorded. Complications were defined as the onset of congestive heart failure (CHF), myocardial infarction (MI), or dysrhythmias requiring cardioversion within seven post-operative days; unplanned or prolonged intensive care unit (ICU) stay due to cardiac cause; and cardiac death. Categorical data were compared using discordant data pairs and binomial distribution, with theta = 0.5. Parametric data were compared using students' t test. All comparisons were two-tailed, with alpha < 0.05 considered significant. RESULTS: 55 patients (32 male, 23 female, mean age 73 yr) with AS (mean aortic valve area 0.9 cm2) were studied. Cases and controls were identical for eight of nine pre-operative risk factors. Differences in perioperative management were found. Cardiac complications occurred in five cases and six control patients (P = 1.00). CONCLUSIONS: The current study, involving 55 patients with AS undergoing non-cardiac surgery, showed no difference in the risk of cardiac complications compared with matched controls. However, the intensification of management in the AS patients may have attenuated the risk in this group. The sample size was adequate to detect a fourfold increase in risk.

Aged↗
PubMed1998

Comparison of radiography, computed tomography and magnetic resonance imaging in the detection of sacroiliitis accompanying ankylosing spondylitis.

OBJECTIVE: To compare magnetic resonance (MR) imaging, computed tomography (CT), and radiography in the detection of sacroiliitis accompanying ankylosing spondylitis (AS). DESIGN AND SUBJECTS: Nine volunteers and 24 patients were recruited. Radiography, CT, and MR imaging were completed within a 1-week period in 24 patients with AS. In precontrast MR examination, spin-echo T1, fast spin-echo T2, and gradient echo with rephasing T2* images were obtained without fat saturation using a 0.3-T imager for all volunteers and patients. Postcontrast MR examination was performed using the same precontrast SE T1 sequence for patients with AS. RESULTS AND CONCLUSIONS: MR imaging directly showed the normal cartilage in all 16 sacroiliac joints of the 8 volunteers. In the 24 patients with AS, cartilage abnormalities were observed in 42 sacroiliac joints. More diagnoses of sacroiliitis were made using MR and CT imaging than using radiography (P < 0.001). Therefore, low-field-strength MR can be useful in detecting early sacroiliitis in patients with AS. MR imaging was able to reveal early cartilage changes and bone marrow edema, which could not be found by either CT or radiography.

Adolescent↗
PubMed1998

Effect of PAF receptor antagonists on adrenocortical secretion induced by ACTH in normal and athymic nude mice.

The effect of SM12502 and CV6209, platelet-activating factor (PAF) receptor antagonists on corticosterone (B) secretion induced by ACTH was examined in the perfused adrenals of CD1 ICR (normal) and CD1 ICR nu/nu (athymic) mice. Bilateral adrenals were perfused in situ with an artificial medium equilibrated by 95% O2 + 5% CO2. Continuous infusion of 10 microM SM12502 or CV6209 inhibited the B response to 100 pg/ml ACTH markedly in normal mice but insignificantly in athymic mice. Infusion of PAF did not significantly affect B secretion in either normal or athymic mice. Administration of 0.1 microM of N-methylcarbamyl PAF, a nonmetabolizable PAF agonist, significantly increased B secretion in normal mice, but not in athymic mice. Infusion of SM12502 significantly depressed the B response to 10 microM forskolin or 1 mM dibutyryl cyclicAMP (cAMP) in normal mice, but not in athymic mice. The results indicate that endogenous PAF and its receptor may play a role in the ACTH-initiated signaling pathway at the phase after responsiveness to cAMP and its receptor may have little function in athymic mice.

Adrenal Cortex↗
PubMed1998

Serum insulin-like growth factors and their binding proteins in patients with hepatic failure and after liver transplantation.

The liver is the major source of circulating insulin-like growth factor-I and -II (IGF-I and IGF-II) and several of their binding proteins (BPs). This study examined the effects of end-stage liver disease (ESLD) and subsequent liver transplantation (LT) on serum levels of these growth factors and their BPs in four children and six adults for up to 2 years. Serum IGF-I and IGF-II were quantified by radioimmunoassay (RIA), IGFBP-3 by immunoradiometric assay (IRMA), and changes in IGFBP-1, -2, -3, and -4 were estimated by Western ligand blotting (WLB). In severe hepatic disease, serum concentrations of IGF-I (10 +/- 5 ng/mL) and IGF-II (126 +/- 32 ng/mL) were significantly (P < .01) less than in normal controls (170 +/- 37 and 590 +/- 41 ng/mL, respectively). One year following LT, the mean levels of IGF-I (344 +/- 55 ng/mL) and IGF-II (627 +/- 38 ng/mL) were within normal limits and remained so for the duration of the study. Patients exhibited considerable variation not only in the rate of achieving normal IGF-I and IGF-II concentrations, but also in the ultimate height and stability of these peptide levels. Serum IGFBP-3 in hepatic failure (580 +/- 140 ng/mL) was significantly (P < .05) lower than in controls (2,900 +/- 220 ng/mL) and increased to normal levels (3,650 +/- 360 ng/mL) 2 to 14 weeks after LT. Serum levels of IGFBP-1, -2, and -4 before and after LT were variable but usually remained within normal limits compared with control sera. The decreases observed in IGF-I, IGF-II, and IGFBP-3 in patients with hepatic failure and their subsequent restoration after LT probably result primarily from the reduced number of functional hepatocytes in ESLD and their subsequent replacement by healthy hepatic tissue. These changes may also result from hormonal alterations and nutritional deficiencies known to exist in patients with severe liver dysfunction, which are corrected by LT. We conclude that LT in patients with severe hepatic insufficiency enhances the potential for normal cell growth and replication by restoring serum IGF-I, IGF-II, and IGFBP-3 concentrations to normal concomitantly with the improvement in hormonal and nutritional status.

Adolescent↗
PubMed1998

Accuracy of ultrasonic pachymetry and videokeratography in detecting keratoconus.

PURPOSE: To compare the accuracy of ultrasonic pachymetry measurements and videokeratography-derived indices in distinguishing keratoconus patients from those with normal eyes. SETTING: A subspecialty cornea practice (Los Angeles, California, USA) and the Keratoconus Genetics Research Project. METHODS: Corneal thickness was measured by ultrasonic pachymetry at the center and inferior margins of the pupil of 142 normal and 99 keratoconus patients The corneal surface topography of patients was studied with the Topographic Modeling System (TMS-1). The videokeratographs obtained were analyzed with a computer program that automatically calculates two indices derived from data points in the central and paracentral cornea: central K and I-S values. Linear discriminant analysis was used to determine the correct classification percentages using pachymetry measurements and indices derived from videokeratography as the independent variables. RESULTS: The range of corneal thickness in normal and keratoconic eyes overlapped considerably. In the discriminant analysis, videokeratography indices provided a 97.5% correct classification rate and pachymetry data, an 86.0% rate (P < .01, McNemar's test). CONCLUSION: Keratoconus is more accurately distinguished from the normal population by videokeratography-derived indices than by ultrasonic pachymetry measurements. This may be due to the large variation in corneal thickness in the normal population or the inability of ultrasonic pachymetry to accurately detect the location of corneal thinning in keratoconus by measuring standard points on the cornea. Pachymetry should not be relied on to exclude or diagnose keratoconus because the false-negative and false-positive rates are unacceptably higher than those obtained by videokeratography.

Cornea↗
PubMed1998

PYY-preferring receptor in the dorsal vagal complex and its involvement in PYY stimulation of gastric acid secretion in rats.

1. Microinjection of peptide YY (PYY, 7-46 pmol) into the dorsal vagal complex (DVC) stimulated gastric acid secretion in urethane-anaesthetized rats. Using a variety of neuropeptide Y (NPY) and PYY derivatives, we characterized the pharmacological profile of the receptor mediating the acid secretory response to PYY. 2. [Pro34]rat(r)/porcine(p)PYY and [Pro34]human(h)PYY (23-117 pmol), microinjected unilaterally into the DVC resulted in a similar maximal increase in net acid secretion reaching 68+/-11 and 89+/-31 micromol 90 min(-1) respectively. 3. Rat/hNPY and pNPY (47 pmol) microinjected into the DVC induced a similar net gastric acid secretion (27+/-8 and 23+/-8 micromol 90 min(-1) respectively) and a higher dose (116 pmol) tended to reduce the response. 4. Pancreatic polypeptide (PP, 4-46 pmol), [Leu31,Pro34]r/hNPY (47 and 117 pmol) and the Y2 selective agonists, hPYY3-36, pNPY5-36 and PNPY13-36 (25-168 pmol) microinjected into the DVC failed to influence basal gastric acid secretion. 5. The rank order of potency of PYY > or = [Pro34]r/pPYY = [Pro34]hPYY> r/hNPY = pNPY to stimulate gastric acid secretion upon injection into the DVC and the ineffectiveness of PP, [Leu31,Pro34]NPY and C-terminal NPY/PYY fragments suggest that a PYY-preferring receptor subtype may be involved in mediating the stimulating effect.

Animals↗
PubMed1998

Differential activation requirements associated with stimulation of T cells via different epitopes of CD3.

A panel of monoclonal antibodies directed to different epitopes of porcine CD3 were employed to investigate stimulation requirements of porcine T lymphocytes. It was found that epitope specificity was an important property of the anti-CD3 antibodies that determined the requirements for T-cell proliferation. Thus, T-cell proliferation induced by triggering different CD3 epitopes showed three different requirements: (a) proliferation induced by the most insensitive epitope required both epitope ligation and some unknown additional signal(s); (b) proliferation induced by the most common epitopes only required epitope ligation, either by monocytes or by immobilization; (c) proliferation induced by the most sensitive epitope required neither epitope ligation nor participation of antigen-presenting cells (APC). These findings may help to explain the previous confusion over the requirements for T-cell activation through the CD3 pathway. Finally, the above conclusions apply only to alpha beta T cells, as porcine gamma delta T cells, either in bulk culture or isolated, did not proliferate in response to anti-CD3 stimulation. Therefore, the mechanism underlying gamma delta T-cell activation may be different from that of alpha beta T cells.

Animals↗
PubMed1998

Prenatal ontogeny of lymphocyte subpopulations in pigs.

Although porcine lymphocytes have been classified into numerous subpopulations in postnatal animals, little is known about the ontogeny of these complex cell subsets. Using double- and triple-colour flow cytometry (FCM), we investigated the surface phenotype of fetal lymphoid cells in the thymus, cord blood, spleen and mesenteric lymph nodes at different stages of gestation. It was found that the major lymphocyte subpopulations started to appear at the beginning of the second third of the gestation period, with B cells being the earliest lymphocyte subpopulation to appear in the periphery. The T-cell receptor (TCR) gamma delta+ cells were the earliest detectable T-cell subset, developing first in the thymus and subsequently arriving in the periphery. Later in ontogeny, however, the number of TCRalpha beta+ lymphocytes rapidly increased, becoming the predominant T cells both in the thymus and in the periphery. Cells with the phenotype of adult natural killer cells were also identified in pig fetuses, though their nature and functional roles remain to be investigated. In addition, CD2 was expressed on most B cells whilst very few CD4+ TCRalpha beta+ cells or CD2+ TCRgamma delta+ cells expressed CD8, suggesting that the expression of CD2 and CD8 may reflect the functional status of the cells in postnatal animals. Taken together, this study has provided a systematic analysis of fetal porcine lymphocyte subpopulations and may provide the base for studies to establish the physiological roles of these lymphocyte subsets.

Animals↗