Biomedical subjects

S Wang

Publications and source records attributed to S Wang.

At least 847 records · Page 47Linked to original sources

PubMed1998

Transdermal delivery of cyclosporin-A using electroporation.

Topical delivery of cyclosporin A (CSA) is desirable for treating psoriasis, but it is hindered by the barrier property of stratum corneum, and the physicochemical properties of CSA. Attempts to deliver CSA from a solution prepared in 40% ethanol (EtOH) is phosphate buffered saline (PBS) using iontophoresis did not result in any significant increase in drug delivery, compared to passive. However, the use of electroporation pulses as a physical penetration enhancer enabled delivery of a significant amount of CSA. Single pulse electroporation study indicated that the amount of EtOH delivered across the skin increased as the applied electrode voltage (Uelectrode) was increased. However, it did not translate into a proportional increase in the delivery of CSA and only a three to four times increase, compared to passive delivery, was seen with the single purse electroporation. The drug contact duration had a varying effect in the efficiency of transdermal delivery of CSA. Four hour contact duration was chosen for the multiple pulse study. Use of multiple pulses (25 pulses, 10 ms each) at Uelectrode 200 V resulted in a sixty-fold increase, compared to passive, in the delivery of CSA to the skin. Transdermally delivered CSA was mostly bound to the skin and only a small amount was seen to cross the full skin into the receiver compartment. In a study of solvent transport, the flux of water was up to three times larger than that of EtOH after electroporation.

Administration, Cutaneous↗

PubMed1998

Apoptosis in mouse embryos: elevated levels in pregastrulae and in the distal anterior region of gastrulae of normal and mutant mice.

The pattern of apoptotic cell death has been surveyed in prestreak and primitive streak embryos of four strains of mice and in three mutants affecting gastrulation. In C57BL/6 embryos, a high level of cell death occurs in the early egg cylinder stage at embryonic day 5 (E5) to E5.5. In all strains, cell death is elevated shortly before gastrulation, but the level varies four- to fivefold among strains. During gastrulation, cell death declines but is relatively more abundant in the distal and distal anterior regions. Early streak embryos cultured in media with reduced levels of growth factors show increased cell death mainly in the distal region. In three mutants with disturbed function of the proximal visceral endoderm and/or primitive streak, cell death is increased, and the regional pattern seen in normal embryos is intensified. The results strongly suggest that the proximal visceral endoderm and primitive streak region are the principal sites of synthesis of growth factors promoting cell survival. We conclude that localized growth factor supply has an important role in regulating the size of the embryo and of embryonic regions.

Animals↗

PubMed1998

Evidence for an early G1 ionic event necessary for cell cycle progression and survival in the MCF-7 human breast carcinoma cell line.

The mechanism of the G0/G1 arrest and inhibition of proliferation by quinidine, a potassium channel blocker, was investigated in a tissue culture cell line, MCF-7, derived from a human breast carcinoma. The earliest measurable effect of quinidine on the cell cycle was a decrease in the fraction of cells in S phase at 12 hr, followed by the accumulation of cells in G1/G0 phases at 30 hr. Arrest and release of the cell cycle established quinidine as a cell synchronization agent, with a site of arrest in early G1 preceding the lovastatin G1 arrest site by 5-6 hr. There was a close correspondence among the concentration-dependent arrest by quinidine in G1, depolarization of the membrane potential, and the inhibition of ATP-sensitive potassium currents, supporting a model in which hyperpolarization of the membrane potential and progression through G1 are functionally linked. Furthermore, the G1 arrest by quinidine was overcome by valinomycin, a potassium ionophore that hyperpolarized the membrane potential in the presence of quinidine. With sustained exposure of MCF-7 cells to quinidine, expression of the Ki67 antigen, a marker for cells in cycle, decreased, and apoptotic and necrotic cell death ensued. We conclude that MCF-7 cells that fail to progress through the quinidine-arrest site in G1 die.

Anti-Arrhythmia Agents↗

PubMed1998

Cloning of a full-length insulin-like growth factor-I complementary DNA in the goldfish liver and ovary and development of a quantitative PCR method for its measurement.

Five forms of insulin-like growth factor-I (IGF-I) complementary DNA (cDNA) were isolated by PCR from goldfish liver and ovary, using primers based on common carp IGF-I sequence. In the goldfish liver, we cloned and sequenced three IGF-I forms (1,2, and 3), and elucidated the full-length cDNA sequence using the 5'-and 3'-RACE. Two IGF-I forms (1 and 2) were cloned from the goldfish ovary and were found to have differences with respect to both size and nucleotide sequence compared to liver IGF-I. The entire liver IGF-I form 1 sequence was found to be 833 nucleotides long, containing a 483-nucleotide open reading from encoding 161 amino acids. The deduced amino acid sequence of the mature peptide was compared to IGF-I sequences of other vertebrates, and found to have 97 and 93% similarity to carp and salmon IGF-I, respectively, In this study we also developed a competitive quantitative PCR method and demonstrated an increase in IGF-I expression following treatments with growth hormone or gonadotropin-releasing hormone in the goldfish liver.

Amino Acid Sequence↗

PubMed1998

The Forbidden Rotational Q-Branch of CH3CF3: Torsional Properties and (A1 - A2) Splittings.

The pure rotational spectrum driven by the small distortion dipole moment perpendicular to the symmetry axis has been investigated between 8 and 18 GHz for CH3CF3 in the ground vibrational state using a pulsed Fourier transform waveguide spectrometer. This molecule has been selected as a prototype for the case of a symmetric top with small ( approximately 500 kHz) torsional energy splittings in the ground torsional state (nu6 = 0). In this state, six (k +/- 3 <-- k) Q-branch series have been measured for lower state K = |k| between 3 and 8 with 27 </= J </= 75. For (nu6 = 1), three series with lower state K between 5 and 7 with 49 </= J </= 66 have been observed. In two of these series, the torsional fine structure extending over approximately 6.8 MHz has been fully resolved. The (A1 - A2) splitting has been measured in the (nu6 = 0) series (K = 6 <-- 3) for 37 </= J </= 74. The global data set of 443 frequencies included avoided-crossing molecular-beam splittings of Meerts and Ozier (1991. Chem. Phys. 152, 241-259) and mm-wave R-branch measurements of Bocquet et al. (1994. J. Mol. Spectrosc. 165, 494-499). In a weighted least-squares analysis, a good fit was obtained by varying 18 parameters in a Hamiltonian that represented both the torsional effects and the sextic splittings. Effective values have been determined for both rotational constants, eight torsional parameters including the barrier height, six diagonal centrifugal distortion constants, and two centrifugal distortion constants (epsilon and epsilonJ) that characterize the (Deltak = +/-3) matrix elements. The difficulties are discussed that arise in defining a unique model for the torsional terms in the Hamiltonian when a high barrier symmetric top is investigated by distortion moment spectroscopy. The redundancies are investigated that exist in the quartic and sextic Hamiltonian for a near-spherical top such as CH3CF3. Copyright 1998 Academic Press.

Journal Article↗

PubMed1998

A novel strategy for introducing exogenous bcl-2 into neuronal cells: the Cre/loxP system-mediated activation of bcl-2 for preventing programmed cell death using recombinant adenoviruses.

We have established a novel strategy for introducing exogenous Bcl-2 into neuronal cells that is mediated by Cre/loxP recombination using recombinant adenoviral vectors. An on/off-switching cassette for Bcl-2 (CALNLbcl-2) was designed to express Bcl-2 by recombinase Cre-mediated excisional deletion of a spacer DNA flanked by a pair of loxP sites. Exogenous Bcl-2 was clearly induced in PC12 cell lines carrying CALNLbcl-2 after infection with recombinant adenovirus producing recombinase Cre (AxCANCre). Dual infection with both AxCANCre and a recombinant adenovirus bearing CALNLbcl-2 showed efficient delivery of exogenous Bcl-2 into a hybrid motoneuronal cell line and primary chicken spinal motoneurons. The delivery of foreign Bcl-2 promoted survival of motoneurons in medium either containing or lacking trophic support. Thus, this strategy for delivery of exogenous Bcl-2 will be useful for studying neuronal death as well as for introducing foreign genes into postmitotic neurons under the control of recombinase Cre.

Adenoviridae↗

PubMed1998

A model for ATM heterozygote identification in a large population: four founder-effect ATM mutations identify most of Costa Rican patients with ataxia telangiectasia.

Ataxia telangiectasia (A-T) is an autosomal recessive disorder with a broad range of clinical manifestations and a frequency of 1:40,000-100,000 live births. Epidemiological studies have suggested that A-T heterozygotes are at an elevated risk of breast cancer. ATM mutations occur worldwide over the entire ATM gene, making it difficult to identify heterozygotes in large populations. However, some founder-effect mutations are specific for certain populations. Here, we present four mutations in Costa Rican A-T patients that accounted for 86-93% of 41 patients studied in two batches. We have developed assays for rapid detection of these four mutations which can be used diagnostically. They will also enable the Costa Rican population to be used as a model for analyzing the role of ATM heterozygosity in cancer development and other disorders.

Ataxia Telangiectasia↗

PubMed1998

Treatment of rats during pubertal development with 2,3,7,8-tetrachlorodibenzo-p-dioxin alters both signaling kinase activities and epidermal growth factor receptor binding in the testis and the motility and acrosomal reaction of sperm.

Different doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.1, 1, 5, and 10 micrograms/kg body wt) were administered i.p. to 21-day-old male Sprague-Dawley rats. Control animals received the same volume of the vehicle (acetone:corn oil, 1:19). Body weight and daily food intake were recorded during the 90-day time course of the study. Random samples of five rats were sacrificed at 34, 49, 62, and 90 days of age. Epidermal growth factor receptor (EGFR) in whole testis was measured, as were the activities of c-Src kinase, protein tyrosine kinase (PTK), mitogen-activated protein 2 kinase (MAP2K also termed as Erk2), protein kinase A (PKA), and protein kinase C (PKC). Testicular tissue from 90-day-old rats was evaluated for histopathology, and sperm numbers in whole testis were counted to estimate daily sperm production. The motility of sperm in the vas deferens and caudal segments of the epididymis of 90-day-old rats was measured by computer assisted sperm analysis (CASA) and the function of the sperm was tested by assessment of acrosome reactions. A dose of 10 micrograms/kg resulted in testicular atrophy and histopathologic examination revealed a decrease in the diameter of the seminiferous tubules. Sertoli cell nuclei were clearly seen, but the spermatogonial population was totally absent. Lower doses of TCDD did not affect testicular histology, but doses as low as 1 microgram/kg significantly decreased testicular sperm numbers and affected some sperm functions (motility parameters and acrosome reactions) in 90-day-old rats. Significant decreases in EGFR were found in 34-day-old rats and this effect on EGFR was sustained until the end of the experiment (90 days). Although TCDD significantly increased c-Src kinase activity in immature and mature rats, opposite effects of TCDD on activities of PTK, PKA, and PKC were found in 34-day-old rats vs 49-, 62-, and 90-day-old rats. When 10 micrograms TCDD/kg was administered to 21-day-old rat, 24-h after c-Src kinase inhibitor geldanamycin, there was no testicular atrophy and no change in the daily sperm production was found. These findings provide evidence for involvement of Src kinase signaling and EGFR in the mechanism by which TCDD disrupts testicular development and subsequently affects testis function.

Acrosome↗

PubMed1998

Toxic metals stimulate inflammatory cytokines in hepatocytes through oxidative stress mechanisms.

Hepatocytes, as well as nonparenchymal cells, secrete proinflammatory cytokines and chemokines that are involved in the pathology of many liver diseases. In particular, tumor necrosis factor-alpha (TNFalpha), as well as members of the CXC family of chemokines, including interleukin (IL)-8 in humans and macrophage inflammatory protein (MIP)-2 in rodents, have been implicated in both damage and repair processes associated with various hepatotoxins. In the liver, cytokine secretion is usually associated with nonparenchymal cells, particularly Kupffer cells. In the present studies, cytokine gene expression and secretion were investigated in hepatocytes treated with cadmium chloride (CdCl2) or vanadium pentoxide (V2O5). Using human Hep G2 cells and freshly isolated rodent hepatocytes, it was demonstrated that metals increase gene expression and secretion of CXC chemokines and TNFalpha. IL-8 and MIP-2 secretion induced either by the metals or H2O2 were inhibited by antioxidants such as tetramethyl-thiourea and N-acetyl-cysteine. In vitro neutralization experiments with TNFalpha and in vivo studies with TNFalpha receptor knockout mice indicated that the metals directly stimulate CXC chemokine secretion without the need for TNFalpha. Taken together these studies indicate that, in addition to other inflammatory mediators and acute phase proteins, cytokines and chemokines are produced by hepatocytes, which may participate in hepatotoxic responses. The events responsible for their expression involve cellular redox changes.

Animals↗

PubMed1998

Cardiokymograph system with a capacitance transducer and its preliminary application in the measurement of heart wall movement.

A novel cardiokymograph system is introduced. The new system features a capacitance transducer with increased sensitivity and can be used in multichannel measurements. The novelty of this technique is the injection of a current into the patient coupled with the use of a capacitive displacement transducer and the possibility of multichannel monitoring. It provides for the possibility of removing breath noise when some signal processing technique, such as adaptive filtering, is used. Further investigation is needed to demonstrate clinical significance and pathologies.

Adult↗

PubMed1998

Clinical study of multi-drug resistance gene (MDR1) expression in primary ovarian cancer.

This study was designed to measure the multi-drug resistance gene (MDR1) mRNA content and analyze clinical relationship between MDR1 expression and drug resistance in primary ovarian cancer. Reverse transcription PCR (RT-PCR) was used to measure MDR1 mRNA content in biopsy sample of 31 primary ovarian cancers (experimental group) and 30 gynecological tumors (control group). The level of 95.2% (20/21) MDR1 expression was relatively low, and the detected rate of MDR1 expression was 67.7% (21/31) in experimental group, which was higher than that in control group (40.0%, P < 0.05). The differences of MDR1 expression between the effective group and no effect group after combined chemotherapy was significant (P < 0.05). No significant relationship was found between MDR1 expression and clinical stage or histological classification or grade of differentiation in experimental group. We are led to concluded that primary ovarian cancers have drug-resistance clones which might express MDR1 spontaneously and expression of MDR1 may be used as a prognostic and predictive indicator for clinical response of ovarian cancers to combined chemotherapy.

Adolescent↗

PubMed1998

Clinical implication of serum sIL-2R levels in ovarian cancer.

The levels of serum soluble interleukin-2 receptor (sIL-2R) of 36 patients with ovarian cancer, 34 with benign gynecological tumors and 31 blood donors were measured by ELISA. Compared to those of benign and normal controls, serum levels of sIL-2R in patients with ovarian cancer elevated significantly (P < 0.01). Serum sIL-2R levels were likely related to types, clinical stage or histological grading of ovarian cancer. We were led to conclude that serum sIL-2R level may reflect the status of the immune system and the disease severity in patients with ovarian cancer. Its value as a marker for monitoring treatment and prognosis needs further studies.

Adolescent↗

PubMed1998

Differential effects of bone mineral content and bone area on vertebral strength in a swine model.

Since the biomechanical competence of a vertebral body may be closely related to the content and distribution of the bone mineral, we have evaluated the effects of projected vertebral bone area (BA) and bone mineral parameters [bone mineral content (BMC) or bone mineral density (BMD)] on their biomechanical competence. We used dual-energy X-ray absorptiometry (DXA) to assess the bone mineral parameters of 36 swine thoracic vertebrae (T1-T12) and 15 lumbar vertebrae (L1-L5) after removal of the posterior elements. The failure load, compressive stress, and the stored strain energy of these vertebral bodies were assessed by a uniaxial compressive test using an MTS 810 testing system. Multiple regression analysis showed a significantly negative effect of BA and significantly positive effect of BMC on the biomechanical competence (compressive stress, r2 = 0.67, P < 0.0001; failure load, r2 = 0.75, P < 0.0001). However, the stored strain energy was only related to the BMC (r2 = 0.35, P < 0.0001). The contributory effects of BMC and BA on the biomechanical competence were not equal. The effects of BMC was larger than BA in determining the failure load and stored strain energy, whereas the reverse was found for the compressive stress. Using the log-transformed parameters as the regressors resulted in similar results. These results suggested the differential effects of BA and BMC in determining the biomechanical competence of vertebral bodies. We recommend the use of both parameters instead of BMD alone for evaluation of the vertebral biomechanical competence.

Absorptiometry, Photon↗

PubMed1998

A common local anesthetic receptor for benzocaine and etidocaine in voltage-gated mu1 Na+ channels.

According to Hille's modulated receptor hypothesis, benzocaine shares a common receptor with all other local anesthetics (LAs) in the voltage-gated Na+ channel. We tested this single receptor hypothesis using mutant muscle Na+ channels of mu1-I1575A, F1579A, and N1584A transiently expressed in Hek-293t cells. Both benzocaine and etidocaine are more effective at blocking mu1-N1584A current than the wild-type current, while they are less potent at blocking mu1-F1579A current. Such concurrent changes of both benzocaine and etidocaine potency towards F1579A and N1584A mutants suggest that they share a common LA receptor. Consistent with results found in studies of native Na+ channels, permanently charged QX-314 at 1 mM is not effective at blocking wild-type, F1579A, and N1584A current via external application. In contrast, QX-314 is relatively potent at blocking I1575A current when applied externally. This increased potency of external QX-314 against the mu1-I1575A mutant has been reported previously in a study of the brain counterpart. Mutant I1575A also appears to be highly sensitive to the external divalent cation Cd2+, probably because of the presence of cysteine residues near the mu1-I1575 position in the IV-S6 segment. To our surprise, neutral benzocaine becomes more effective at blocking mu1-I1575A current than the wild-type current, whereas the opposite is found for etidocaine. We hypothesize that an increase in accessibility of external QX-314 to the mu1-I1575A mutant is accompanied by a reduction of binding towards the charged amine component.

Amino Acid Sequence↗

PubMed1998

Coronary calcium and standard risk factors in symptomatic patients referred for coronary angiography.

OBJECTIVES: The purpose of this study was to compare quantitative estimates of coronary calcification with traditional coronary risk factors to determine their independent predictive power for the diagnosis of obstructive angiographic coronary artery disease in symptomatic patients. METHODS: Three hundred sixty-eight symptomatic patients underwent coronary angiography and electron beam computed tomography at four different centers between April 1989 and December 1993. A blinded cardiologist interpreted the electron beam computed tomograms. Coronary risk factors were obtained in all 368 patients. Both bivariate and multivariate analyses were used to investigate the relation between risk factors and angiographic disease. RESULTS: One hundred fifty-eight patients (43%) had angiographically obstructive coronary artery disease (>50% luminal stenosis) and 297 (81%) had coronary calcification. At the bivariate level, only male sex and log-transformed coronary calcification were predictive of angiographic disease (p = 0.008, p = 0.001). By multivariate analysis, only male sex and coronary calcification were predictive (p = 0.001, p = 0.001). Sixty-four of the 71 patients without coronary calcification did not have disease, yielding a negative predictive value of 90%. Receiver operating characteristic curve analysis showed that the amount of coronary calcium was a significantly better discriminator of disease than were the other risk factors. CONCLUSIONS: Coronary calcification is a stronger predictor of angiographic coronary artery disease in symptomatic patients undergoing angiography than are standard risk factors.

Aged↗

PubMed1998

TACHY: an expert system for the management of supraventricular tachycardia in the elderly.

PURPOSE: Many physicians find the management of supraventricular tachyarrhythmia (SVT) in the elderly complex and challenging. With the use of artificial intelligence theory, we developed an interactive computer expert system, TACHY, to recommend therapies and warn physicians of potential therapeutic side effects. METHODS: We developed a knowledge base that stores guidelines for the management of SVT in the elderly. After the diagnosis of current SVT was input into the computer, TACHY generated a list of therapeutic options as hypotheses. TACHY then prompted the user to provide current patient-specific clinical information, and the optimal therapeutic option was then selected. Potential therapeutic side effects were also displayed. TACHY was tested in a retrospective and a prospective study. The retrospective study, comprising 96 patients with 126 episodes of SVT, was performed to determine the concordance of therapy between TACHY and cardiologists. A prospective study in 18 patients with 26 episodes of SVT was also performed to validate TACHY's recommendations in restoring sinus rhythm. RESULTS: In the retrospective study the concordance between TACHY and the cardiologist's first therapeutic option was 95.9% (121 of 126 episodes). In the prospective study sinus rhythm was restored in 18 (69%) of 26 episodes of SVT by the first therapeutic option recommended by TACHY. In the remaining eight episodes use of the second or third suggestion of TACHY was successful in controlling the ventricular response to SVT. No adverse reaction to the therapeutic options suggested by TACHY occurred. CONCLUSION: TACHY, a knowledge-based computer expert system that simulates human decision making, produced promising results in the management of SVT in the elderly.

Aged↗

PubMed1998

The role of cell cycle regulatory proteins, cyclin D1, cyclin E, and p27 in thyroid carcinogenesis.

The cell cycle is controlled in part by cyclin-dependent kinases (CDKs), which are activated by forming complexes with cyclins. CDKs phosphorylate certain substrates to facilitate the proliferating cells through the cell cycle. CDK inhibitors (CDKIs) such as p27 inhibit cyclin-CDK complexes and function as a negative cell cycle regulator. The overexpression of the positive regulators (cyclins) or the underexpression of the negative regulators including p27 has been seen in a variety of neoplasms, but their role and interaction in thyroid carcinogenesis is yet to be established. We studied the expression of cyclins D1 and E, and the CDKI, p27 by immunohistochemistry in 116 cases, including 59 cases of follicular variant of papillary carcinoma (FVPC) and 57 cases of follicular adenoma (FA). The positive staining was divided into four grades: 1+ if less than 10%, 2+ if 11% to 25%, 3+ if 26% to 50%, and 4+ if greater than 50% of the nuclei of tumor cells stained positively. Cyclin D1 expression was seen in 37 (63%) FVPC and 34 (60%) FA. Cyclin E-positive cells were seen in 51 (86%) FVPC and 47 (82%) FA. No significant differences in the grade of cyclins D1 (P = .261) and E (P = .284) staining was seen between FVPC and FA. Of the 59 FVPC, 53 (89%) showed p27-positive cells; of these, 33 were 1+, nine were 2+, seven were 3+ and only four were 4+ positive. Conversely, all 57 FA were p27 positive, 53 were 4+, and four were 3+ positive. This difference in the grade of p27 staining between FVPC and FA was statistically significant (P < .001). This study shows a significant underexpression of p27 in FVPC compared with FA, suggesting that a decrease in p27 expression plays a more important role than overexpression of cyclins D1 and E alone in thyroid carcinogenesis and that p27 immunostaining may be helpful in the diagnosis of FVPC.

Adenocarcinoma, Follicular↗

PubMed1998

Neonatal withdrawal following pre- and postnatal exposure to methadone in the rat.

Recent evidence has shown that infant rats undergo precipitated withdrawal following chronic postnatal injection of morphine. In this study we examined whether or not infants exposed to methadone prenatally via the placental blood supply and postnatally via the dam's milk would also experience precipitated withdrawal. Dam's were implanted on gestational day 14 with osmotic minipumps containing one of two concentrations of methadone to supply the opiate throughout gestation and the first postnatal week. Nontreated and pair-fed controls were used. On postnatal day 7, pups were injected with naltrexone and their locomotor activity and ultrasonic vocalizations measured. Methadone exposed pups were more active and vocalized more when injected with naltrexone than with saline. The controls did not show these behavioral changes. The milk of methadone-exposed dams apparently contains sufficient quantities of the opiate for dependence to develop. The results are consistent with other data that demonstrate that very young rat pups can experience an opiate abstinence syndrome that includes increased behavioral activation.

Animals↗