Biomedical subjects

S C Hsieh

Publications and source records attributed to S C Hsieh.

At least 19 recordsLinked to original sources

PubMed1999

Prior treatment experience related to process and outcomes in DATOS.

Using data collected from cocaine-abusing patients who participated in the Drug Abuse Treatment Outcome Studies (DATOS), we contrasted patients in treatment for the first time and patients having extensive histories of prior treatment to identify factors associated with better outcomes in each group. Compared with first-timers, treatment-experienced patients had less favorable post-treatment outcomes. Indicators of early engagement in DATOS treatment predicted post-treatment abstinence for both groups. Importantly, the interaction of treatment history and several process measures affected post-treatment abstinence. For example, individual counseling and program compliance had greater impacts on abstinence among treatment repeaters in outpatient drug-free programs than for first-timers. Social support and environmental context were significantly related to abstinence. These findings confirm the importance of considering treatment process and aftercare in developing and implementing strategies to optimize treatment for patients with different treatment histories.

Adult↗

PubMed1998

Pulse application of platelet-derived growth factor enhances formation of a mineralizing matrix while continuous application is inhibitory.

Platelet-derived growth factor (PDGF) stimulates chemotaxis and proliferation of osteoblasts, and induces bone formation in vivo. To determine how PDGF might regulate these cells, the effect of PDGF on long-term mineralizing cultures of fetal rat osteoblastic cells was examined. Although PDGF increased cell proliferation in these cultures, continuous treatment with PDGF caused a dose-dependent decrease in mineralized nodule formation. When cells were treated with multiple, brief (1 day) exposures to PDGF at the osteoblast differentiation stage, there was a significant 50% increase in mineralized nodule area. Based on modulation of alkaline phosphatase activity it appears that longer-term exposure to PDGF reduces mineralized nodule formation largely by inhibiting differentiated osteoblast function, while short-term exposure enhances proliferation without inhibiting the differentiated phenotype. Thus, the ultimate affect of PDGF on bone formation is likely to reflect two processes: a positive effect through enhancing cell number or a negative effect by inhibiting differentiated function. The inhibitory effect of PDGF on formation of a mineralized matrix is unlikely to be simply a result of enhanced proliferation of "fibroblastic" cells since cultures treated with PDGF for 3 days and then transferred to new plastic dishes exhibited a 70% increase in mineralized nodule area compared to controls. These results would predict that multiple, brief exposures to PDGF would enhance bone formation in vivo, while prolonged exposure to PDGF, which is likely to occur in chronic inflammation, would inhibit differentiated osteoblast function and limit bone regeneration.

Animals↗

PubMed1998

Usefulness of electron beam computed tomography in children with heterotaxy syndrome.

Children with heterotaxy syndrome frequently have complex cardiac and noncardiac malformations requiring detailed diagnostic evaluation for management planning. Direct delineation of these structures by electron beam computed tomography (EBCT) is validated as a means of diagnosis. From July 1995 to March 1997, 32 patients (16 girls, 16 boys) with clinically impressed heterotaxy syndrome were enrolled in this study. After evaluation by echocardiography, EBCT studies were performed. Interpretation of cardiac anomalies was performed by sequential analysis based on these cross-sectional images. The diagnoses were subsequently confirmed by angiocardiography and surgical findings. Twenty-eight patients had bilateral trifurcated bronchi, and most of these (24 of 28) did not have a spleen. Four patients had bilateral bifurcated bronchi, 2 patients had polysplenia, and the other 2 patients had a lobulated single spleen. We found that laterality could be identified by EBCT in all patients. Comparison of diagnostic yield between echocardiography, catheterization, and EBCT showed that EBCT is superior to echocardiography and catheterization in demonstration of pulmonary venous anatomy and presence of a very small rudimentary ventricle. In addition, associated visceral, bronchopulmonary, mediastinal, and intracardiac anomalies could all be clearly delineated by EBCT at the same time. Thus, EBCT is a promising complementary modality for an overall understanding of heterotaxy syndrome.

Abnormalities, Multiple↗

PubMed1998

A regression analysis estimating the number of drug-using arrestees in 185 US cities.

OBJECTIVES: This study sought to provide population-based estimates of drug-using arrestees in the 185 largest US cities. METHODS: A prevalence model for drug-using arrestees was developed by relating selected social indicators (from 1990 census data) and drug use rates (from Drug Use Forecasting program data) via logistic regression analysis. RESULTS: It was estimated that in 1990, across the 185 cities, about 925,000 arrestees used cocaine, 317,000 used opiates, 213,000 used amphetamines, 389,000 were drug injectors, and 1,296,000 used an illicit drug. CONCLUSIONS: This approach represents a cost-efficient method for prevalence estimation based on empirically demonstrable relationships between social indicators and drug use rates.

Adolescent↗

PubMed1997

The expression of genes modulating programmed cell death in normal human polymorphonuclear neutrophils.

Normal human polymorphonuclear neutrophils (PMN) have a short life and die in progression via apoptosis. In order to understand the molecular basis of PMN apoptosis, the expression of apoptosis-related (Fas, Fas-ligand, p53, and c-myc) and survival-related (bcl-2) genes was detected by flow cytometry, Western blot and reverse transcription-assisted polymerase chain reaction (RT-PCR). We found that Fas and Fas-ligand (FasL) were expressed on the surface of most of the cells. However, the disappearance of FasL was much faster than Fas after 24 h incubation. p53 and bcl-2 were also expressed in the cytoplasm of most of the cells. In contrast, the expression of c-myc was negligible in PMN. The addition of monoclonal anti-human Fas antibody (25 micrograms/ml) to PMN suspension enhanced whereas anti-FasL antibody (25 micrograms/ml) suppressed PMN apoptosis in 48 h incubation. These results suggest that the activation of Fas pathway induced by Fas-FasL interaction among PMNs is one of the mechanisms for spontaneous PMN apoptosis. Lack of proto-oncoprotein c-myc expression in PMN is responsible for their non-proliferative property and may aggravate the spontaneous apoptosis of the cells.

Animals↗

PubMed1997

Tamm-Horsfall glycoprotein (THG) is a binder for surface membrane proteins on blood cells and glomerular mesangial cells.

A macromolecule with a molecular weight of 90-100 kDa was purified from normal human pregnancy urine. The molecule was proved to be the Tamm-Horsfall glycoprotein (THG) by Western blot analysis. The macromolecule contains carbohydrate as detected by an enzyme immunoassay. Functionally, the glycoprotein can adhere to and stimulate the thymidine incorporation of human mononuclear cells (MNC) in modest degree via its membranotropic property. In addition to MNC, the protein can also bind to the surface of human polymorphonuclear neutrophils (PMN), red blood cells (RBC) and rat glomerular mesangial cells (RMC). Western blot analysis of various cell lysates with/without proteinase K pretreatment before cell lysis revealed that a 60 kDa and a molecule larger that 94 kDa on the surface of PMN, a 60 kDa protein on MNC and a 32 kDa protein on RBC are the binding molecules for THG. In contrast, many proteins on the surface of RMC could be bound by THG. Immunoprecipitation of membranous iodinated MNC lysates also confirmed that the 60 kDa molecule on MNC is the binding protein for THG. A number of monosaccharide including N-acetylneuraminic acid, N-acetyl-galactosamine, N-acetyl-glucosamine and alpha-methyl-D-mannoside could not inhibit the mitogenic effect of THG on human mononuclear cells. These results suggest that THG is capable of reacting with surface membrane proteins on different cells, but not through the specific carbohydrate-containing lectin-like receptors on the cell surface.

Animals↗

PubMed1997

Temporal expression of PDGF receptors and PDGF regulatory effects on osteoblastic cells in mineralizing cultures.

Platelet-derived growth factor (PDGF) is mitogenic and chemotactic for osteoblastic cells in vitro. It is expressed during osseous wound healing and stimulates formation of new bone in vivo. PDGF stimulates cells by binding to specific cell surface receptors. The purpose of this study was to examine the effects of PDGF on osteoblastic proliferation and differentiation in long-term mineralizing cultures. Utilizing Northern blot analysis, we found that continuous PDGF treatment increased histone expression, indicative of enhanced proliferation, but suppressed osteoblast differentiation, demonstrated by inhibition of alkaline phosphatase, type I collagen, and osteocalcin expression. The inhibitory effect of PDGF on the differentiated function of osteoblasts was further established by findings that PDGF significantly inhibited nodule formation. The expression of PDGF receptors varied at different stages of culture. PDGF receptor mRNA expression increased when the cells had achieved a mature phenotype, during the stage of matrix maturation, and then decreased. However, as demonstrated by thymidine incorporation assays, the capacity of PDGF to stimulate DNA synthesis actually decreased during osteoblast maturation, as receptor expression increased. To investigate this apparent contradiction, tyrosyl phosphorylation and immunoblot assays were performed to assess changes in PDGF activation of their cognate receptors. The pattern of PDGF-induced tyrosyl phosphorylation remained relatively constant. This suggests that the diminished mitogenic activity of PDGF that occurs after osteoblast differentiation is regulated at a postreceptor level.

Animals↗

PubMed1997

Rapid detection of Mycobacterium tuberculosis in various clinical specimens by using polymerase chain reaction combined with a nonradioactive hybridization system.

A DNA amplification system using the polymerase chain reaction (PCR) combined with a nonradioactive digoxigenin-labeled probe hybridization was employed to detect Mycobacterium tuberculosis in clinical specimens. One hundred and thirty specimens were tested by several methods including routine culture method, acid-fast staining, BACTEC 460 detection system, PCR, and PCR-hybridization techniques. Sixteen out of 130 specimens were culture positive on Middlebrook 7H11 agar, 10 were positive with acid-fast staining, 18 were positive with BACTEC 460 detection system, 23 were positive with PCR technique, and 62 were positive with PCR-nonradioactive hybridization technique. When compared with culture results, PCR-nonradioactive hybridization had an overall sensitivity of 100% (16/16) and a specificity of 59.7% (68/114). However, 28 out of 46 (60.9%) PCR-nonradioactive hybridization positive specimens which were culture negative had clinical data supporting the diagnosis of tuberculosis. In addition, 4 specimens which were negative by routine culture but positive by BACTEC 460 detection system and two specimens which were negative by routine culture but positive by acid-fast staining were all positive by PCR-hybridization technique. These data suggest that routine culture method may not be sensitive enough to detect M. tuberculosis in all kinds of clinical specimens. Taking this deviation into account, the specificity of PCR-nonradioactive hybridization technique may be rectified range from 63% (68/108) to 79.1% (68/86). PCR itself is not satisfactory enough to detect M. tuberculosis in specimens (the sensitivity and specificity were 56.3% and 87.7%, respectively) in this study. However, when it combines with DNA hybridization technique, they can be a very powerful and rapid diagnostic tool to detect M. tuberculosis in clinical specimens.

DNA, Bacterial↗

PubMed1996

The expression of acidic ribosomal phosphoproteins on the surface membrane of different tissues in autoimmune and normal mice which are the target molecules for anti-double-stranded DNA antibodies.

Affinity-purified polyclonal anti-double-stranded DNA (anti-dsDNA) antibodies from patients with systemic lupus erythematosus (SLE) exert a cytostatic effect on cultured rat glomerular mesangial cells (MC). The cognate antigens expressed on the surface of MC have been proved to be acidic ribosomal phosphoproteins (P proteins) in our previous study. The mesangial cytostatic effect of anti-dsDNA antibodies is attributed to the cross-reactivity of the antibodies with membrane-expressed P proteins, but not to the effect of minute amounts of anti-ribosomal P proteins antibodies contained in the anti-dsDNA preparations. Immunofluorescence staining of the native cells demonstrated that anti-dsDNA antibodies bound to the surface of rat mesangial cells, rat brain astrocytes (RBA-1) and mouse fibroblasts (3T3). Anti-dsDNA antibodies also exert potent cytostatic effects on these cells in a dose-dependent manner. In addition, the plasma membranes of different cell lines and tissues from normal and autoimmune mice were isolated and probed by anti-dsDNA antibodies in Western blot analysis. We found the actively proliferating cells such as MC, RBA-1 and 3T3 may express both P0 (38,000 MW) and P1 (19,000 MW) on the surface membrane. In addition, the kidney, liver and spleen from either autoimmune MRL-lpr/lpr or BALB/c mice may constantly express P0 protein, but the expression of P1 is inconsistent. In contrast, brain and muscle from either mice failed to express P proteins on their surface. Unexpectedly, a high molecular weight substance (larger than 205,000 MW) with unknown nature appears in the membrane of brain and muscle tissues in both mice. Immunoprecipitation of the surface-biotinylated MC-lysate by anti-dsDNA antibodies further confirmed that P1 (19,000 MW) and P2 (17,000 MW) are really expressed on the cell surface. These results suggest that P proteins expressed on the surface of different tissues become the targets for anti-dsDNA antibodies mediating pleomorphic tissue damage in patients with SLE.

Animals↗

PubMed1995

Defective spontaneous and bacterial lipopolysaccharide-stimulated production of interleukin-1 receptor antagonist by polymorphonuclear neutrophils of patients with active systemic lupus erythematosus.

Interleukin-1 receptor antagonist (IL-1ra) binds competitively to IL-1 receptors but does not transduce the signal which blocks the biological activities induced by IL-1. In this study, polymorphonuclear neutrophils (PMN) and mononuclear cells (MNC) from the patients with active systemic lupus erythematosus (SLE) (n = 11), inactive SLE (n = 13) and normal individuals (n = 13) were compared for the IL-1ra producing capacity of these cells. PMN and MNC at a concentration of 1 x 10(6) cells/ml were incubated with medium alone (spontaneous) or stimulated with lipopolysaccharide (LPS, 100 ng/ml) for 24 h. The IL-1ra concentration in the supernatants was quantified by ELISA method. Both spontaneous and LPS-stimulated production of IL-1ra by PMN, but not by MNC, of active SLE were significantly lower than that of inactive SLE or normal groups. Prednisolone (1 and 5 micrograms/ml) did not change the production of IL-1ra by normal PMN either spontaneously or LPS-stimulation in in vitro study. Moreover, the IL-1ra producing capacity of PMN in seven active SLE on admission and after intensive immunosuppressive treatment was measured. These results suggest that the defective IL-1ra production by SLE-PMN is relevant to disease activity and may be regarded as a new indicator of disease activity in patients with active SLE.

Adolescent↗

PubMed1995

Abnormal splenic and thymic IL-4 and TNF-alpha expression in MRL-lpr/lpr mice.

The MRL-lpr/lpr and MRL-(++) mice were studied for the expression of cytokines in the spleen, lymph node, thymus, kidney and brain through the reverse transcription-polymerase chain reaction (RT-PCR). The frequencies of IL-4 and TNF-alpha expression in the thymus and spleen were significantly higher in MRL-lpr/lpr mice than in MRL-(++) mice from the age of 17 to 32 weeks. More importantly, IL-4 transcript was demonstrated in the early rather than in the terminal stage of the lupus disease. At the 20th week, MRL-lpr/lpr mice with active disease exhibited higher concentrations of IL-1 alpha, IL-6 and TNF-alpha in serum than MRL-(++) mice. Interestingly, in MRL-lpr/lpr but not MRL-(++) mice, the IL-6 concentration in cultured supernatants of the thymic cells was significantly higher than that of the splenic or lymph node cells. On the other hand, IL-6 and IL-1 beta were expressed in the brain and kidney of MRL-lpr/lpr mice but not of MRL-(++) mice. Cultured MRL-lpr/lpr mesangial cells could also express IL-6 but to a lesser extent. These results suggest that the abnormal splenic and thymic IL-4 and TNF-alpha expression may predispose the development of autoimmune reactions. The expression of IL-1 beta and IL-6 in the brain and kidney may be implicated in the damage of these two organs in MRL-lpr/lpr mice.

Animals↗

PubMed1995

Production of the third component of complement (C3) by peripheral polymorphonuclear neutrophils of the patients with rheumatoid arthritis.

Normal human polymorphonuclear neutrophils (PMN) can spontaneously produce the third component of complement (C3) in in vitro culture as detected by ELISA. This C3-producing capacity of PMN can be augmented by TNF-alpha (20 ng/ml) and bacterial lipopolysaccharide (100 ng/ml), but not by IL-1 beta or IL-8. The C3 production by PMN was found to be temperature dependent and was suppressed by the addition of protein inhibitor. The C3 mRNA in PMN could be detected by reverse transcription assisted polymerase chain reaction (RT-PCR) after TNF-alpha or LPS stimulation for 6 hours. To further understand C3 production by peripheral blood PMN in rheumatoid arthritis (RA), spontaneous and TNF-alpha stimulated production of C3 by peripheral PMN were compared in 15 cases of active RA, 15 inactive RA and 15 normal individuals. We failed to find any significant difference among the three groups. We conclude that PMN plays a negligible role in C3 hypercomplementemia in patients with active RA.

Arthritis, Rheumatoid↗

PubMed1995

Prostaglandin E2 suppresses the expression and release of beta 2-microglobulin from mitogen-activated normal human mononuclear cells.

BACKGROUND: Prostaglandin E2 (PGE2) is a feedback suppressor of immune response. Beta 2-Microglobulin (beta 2M) is part of HLA class I molecule that mediates viral antigen presentation to cytotoxic T lymphocytes as well as graft rejection. It has been known that beta 2M can be synthesized by both stimulated and unstimulated lymphocytes, but it is unknown whether beta 2M can be modulated by PGE2. This investigation aimed to clarify this point. METHODS: Normal human mononuclear cells (MNC) were isolated, stimulated by phytohemagglutinin (PHA), and cultured for 3 days in the presence or absence of PGE2. The culture supernatants were collected and detected for beta 2M concentration by enzyme linked immunosorbent assays (ELISA). The cell pellets were stained indirectly with immunofluorescence for HLA-class I antigen and beta 2M expression on the surface membranes. In addition, the membrane potential of stimulated or unstimulated cells was measured by flow cytometry to evaluate the effect exerted by PGE2. RESULTS: PGE2 at a concentration of more than 1 x 10(-8)M markedly suppressed the expression and release of beta 2M from PHA-stimulated MNC in a dose-dependent manner. Expression of HLA-class I molecule on PHA-stimulated MNC was also suppressed by PGE2. Kinetic study demonstrated that PGE2 began to suppress beta 2M synthesis of PHA-stimulated MNC from the 3rd day of culture. It also inhibited beta 2M release from lymphocytes in mixed lymphocyte reaction. This inhibitory effect was not due to cell death as confirmed by trypan blue exclusion. PGE2 per se exerts negligible effect on membrane potential of MNC but can normalize the depolarized state of the membrane induced by PHA as demonstrated by 3,3'-dihexyloxacarbocyanine iodide stain. CONCLUSIONS: PGE2 down-regulates the production of HLA-class I antigens and beta 2M molecules. This effect is associated with the suppression of cytotoxic T cell function by PGE2 and may be relevant to the underlying mechanism of PGE2 on this population of cells.

Cells, Cultured↗

PubMed1994

Sequential cytogenetic alterations in hamster oral keratinocytes during DMBA-induced oral carcinogenesis.

Using the hamster cheek pouch oral cancer model, we have performed a comprehensive analysis of the cytogenetic changes in hamster oral keratinocytes during 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis. Tumour induction in the hamster cheek pouch required repeated application of the carcinogen for 14 weeks. We have found that this hamster oral cancer model to be suitable for cytogenetic studies. Unlike human oral cancers where chromosome breaks have been shown, this is only infrequently observed in DMBA-treated hamster oral keratinocytes. Of importance is the finding that at the beginning of the second week of DMBA treatment, there is a significant increase of karyotypes demonstrating tetraploid or near-tetraploidy. We propose that the significant increase in hamster oral keratinocytes exhibiting tetraploidy be further evaluated as a marker of premalignancy/malignancy.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1994

Reducing HIV risk behavior among injection drug users: effect of methadone maintenance treatment on number of sex partners.

Some studies have found that sex-related HIV risk behavior is less common among drug users in treatment than among users not in treatment; other studies have found no such relationship. However, past studies have not controlled for drug-user background characteristics that might confound the relationship between treatment and risk behavior. Among this sample of injection drug users in Los Angeles, those enrolled in methadone maintenance treatment report fewer past-year sex partners than those not in treatment; among treatment clients, number of past-year partners is negatively related to time in treatment. These findings persist after age and other background characteristics are controlled. Path analyses suggest that treatment may reduce sex-risk behavior by facilitating clients' disengagement from paid sex and raising their perceived self-efficacy for risk reduction.

Adult↗

PubMed1994

The elevation of plasma DNA in patients with systemic lupus erythematosus is attributable to increased DNA release and defective DNA binding of mononuclear cells.

BACKGROUND: Although immunoprecipitable DNA has been found in a subgroup of patients with systemic lupus erythematosus (SLE) exhibiting systemic vasculitis and/or central nervous system involvement, the mechanism for elevated plasma DNA in these patients is poorly understood. METHODS: The plasma DNA concentrations and reactivity of serum and lymphocytes to six species of double-stranded DNA from calf thymus, human placenta, Escherichia coli, Micrococcus lysodeikticus, Clostridium perfringens and poly (dG.dC). poly (dG.dC) were measured in twenty-seven patients with active SLE. To understand the mechanism of increased plasma DNA in SLE, the DNA binding and release of the mononuclear cells were examined. RESULTS: Compared with the controls, the incidence of the presence of plasma DNA was markedly increased in SLE (59.3% in SLE vs. 7.4% in controls) as detected by counterimmunoelectrophoresis. Except for DNA from Clostridium perfringens, the reactivity of lupus sera to various DNA samples was significantly higher than that of the controls. The reactivity of lymphocytes to 6 species of DNA (as defined by 3H-thymidine incorporation of the cells) was also higher in SLE patients. In DNA binding and releasing experiments, patients with SLE were found to have decreased 3H-DNA binding activity (0.169 +/- 0.018 micrograms/2 x 10(6) cells in SLE vs. 0.283 +/- 0.02 micrograms/2 x 10(6) cells in controls, p = 0.001) but to have increased spontaneous release of DNA (1,465 +/- 412 cpm in SLE vs. 630 +/- 179 cpm in controls, p = 0.0173) in mononuclear cells. CONCLUSIONS: The results suggest that some subsets of lymphocytes can be sensitized by different DNA samples in vivo to increase endogenous DNA release from mononuclear cells, which in addition to decreased DNA clearance as has been previously reported, may be responsible for the elevation of plasma DNA in patients with SLE.

Adult↗

PubMed1993

Unrecognized cocaine use among schizophrenic patients.

OBJECTIVE: Unrecognized stimulant use could lead to the misdiagnosis of schizophrenia or the misunderstanding of its course and prognosis. This study was conducted to determine the prevalence of unrecognized stimulant use among patients with a clinical diagnosis of schizophrenia. METHOD: The subjects were 108 schizophrenic patients admitted consecutively to a Veterans Affairs psychiatric hospital. Admitting psychiatrists supplemented routine clinical evaluations with a semistructured interview regarding recent and lifetime use of alcohol, cocaine, amphetamine, marijuana, and opiates. A urine specimen was assayed for the four illicit drugs. RESULTS: Of the 103 patients who provided a urine specimen, 37 (36%) used cocaine during the 6 months before admission, including 31 who used the drug in the week before admission. Because of the poor reliability of negative self-reports of recent cocaine use, clinicians failed to recognize cocaine use in one-third of the patients with a urine toxicology positive for cocaine metabolites. Two other groups of patients were identified; schizophrenic patients without substance abuse (including alcohol) and schizophrenic patients with substance abuse other than stimulants. Both substance-abusing groups were younger than the nonabusing group, but the three groups had similarly high rates of recent psychotic symptoms, homelessness, and unemployment. CONCLUSIONS: Among schizophrenic patients who require hospitalization, clinicians should not rely solely on self-reported stimulant use. Recognition of stimulant use could be improved through routine urine toxicologies for all psychotic patients. The authors suggest that recognition of stimulant use among schizophrenic patients may identify a population with a better prognosis for schizophrenia and different treatment needs.

Adult↗

PubMed1993

Drug-related HIV risk behaviors and cocaine preference among injection drug users in Los Angeles.

Based on a 1988-91 sample of 422 drug-using arrestees in Los Angeles, this study compares the drug-related risk behavior of users whose preferred injection drug is cocaine and users with a preference for heroin or no preference between the two drugs. Cocaine preference is unrelated to the likelihood of needle sharing overall, needle sharing with strangers, needle sharing at shooting galleries, and failure to use bleach as a needle disinfectant. In analyses restricted to users who reported needle sharing, the frequency of sharing is no more closely related to heroin injection frequency than to cocaine injection frequency. These results suggest that local preventive education programs do not need to address distinctive patterns of drug-related risk behavior among injection cocaine users and injection heroin users in Los Angeles.

Adult↗