Biomedical subjects

C S Chung

Publications and source records attributed to C S Chung.

At least 55 records · Page 3Linked to original sources

PubMed1999

Sedimentary fluxes of 90Sr, 137Cs, 239,240Pu and 210Pb in the East Sea (Sea of Japan).

Sediment cores collected from the deep basins of the East Sea (Sea of Japan) provide an ongoing and historical record of artificial radionuclides contamination into one of the most highly publicized radioactive waste dumping areas in the world ocean. The depth distributions of 90Sr, 137Cs and 239,240Pu in sediment cores were investigated with the aid of 210Pb-derived sediment accumulation and mixing rates in the deep basins of the East Sea (Sea of Japan). Five box core samples were collected from the northern Yamato Ridge, Korea Plateau, Ulleung and Japan Basins below 1000-m depth. Sediment inventories of 137Cs and 239,240Pu are inversely correlated with water depth and linearly correlated with sediment accumulation rates. The inventories of these nuclides are linearly correlated with the accumulation rates of organic carbon in sediments. The 238Pu/239,240Pu activity ratios in sediments are 0.036 +/- 0.009 suggesting that most of the Pu to the study area is derived from the global fallout. The activity ratios of 239,240Pu/137Cs, and 90Sr/137Cs in bottom sediments are much lower than those of global fallout due to the differences of particle affinity and biological uptake of these nuclides. Sediment inventories of 90Sr and 137Cs constitute < 4% of the anticipated inventories from the global fallout, while those of 239,240Pu constitute 30-150% of the anticipated inventories from the global fallout. The residence time of the dissolved 239,240Pu in the study area is estimated to be 200-400 years based on the sediment inventory and/or sediment accumulation rate, and water column inventory.

Cesium↗

PubMed1999

Motor perseverative behavior on a line cancellation task.

OBJECTIVES: To study the behavioral and neuroanatomic characteristics of perseverative behavior encountered on a target cancellation task in patients with neglect. METHODS: Motor perseverative behavior during line cancellation task was evaluated retrospectively in 60 patients with left hemispatial neglect from right hemispheric stroke. RESULTS: More than 30% of the patients (21 of 60) showed perseveration, manifested as either repetitive cancellation of the same target (18/21) or cancelling extra lines created by the patients themselves (3/21). Neglect severity correlated positively with the frequency of perseverative errors. Perseveration was most prominent in the rightmost portion of the array. Anterior lesions or massive lesions involving anterior and posterior regions were more likely to be associated with motor perseveration than were lesions restricted to posterior areas. CONCLUSIONS: Although the mechanism of motor perseveration remains to be elucidated, our findings suggest that the combination of aberrant approach behaviors associated with frontal lobe injury and an attentional or intentional bias toward the rightsided targets might explain the behavior.

Adolescent↗

PubMed1999

Splenic immune suppression in sepsis: A role for IL-10-induced changes in P38 MAPK signaling.

BACKGROUND: Studies have indicated that following the induction of sepsis, there is a late (24 h) generalized suppression of the immune response which is associated with increased anti-inflammatory mediator release (e.g., IL-10). However, the mechanisms by which this occurs are unknown. In this regard, recent studies indicate that p38 mitogen-activated protein kinase (p38 MAPK) may play a central role in transducing the signals from immunosuppressive agents which in turn may alter lymphoid cytokine release. The aim of this study, therefore, was to determine whether the anti-inflammatory mediator IL-10 alters splenocyte IL-2 and IFN-gamma release, as well as the expression and activation of p38 MAPK in septic animals. MATERIALS AND METHODS: Splenocytes (SPL) (or for some experiments purified T cells) were harvested from mice subjected 24 h earlier to either sepsis by cecal ligation and puncture (CLP) or Sham-CLP and stimulated with 2.5 microg concanavalin A (ConA)/ml in the presence or absence of either monoclonal antibody (Mab) to IL-10 (4 microg/ml) or IgG control. In subsequent studies, sepsis was induced in C57BL/6J and C57BL/6 IL-10 knockout mice, and SPL harvested and stimulated with ConA. SPL cytokine release was measured by ELISA, and the expression and phosphorylation of p38 MAPK were measured by Western analysis. RESULTS: The results indicate that Th1 cytokine (IL-2, IFN-gamma) release was depressed by sepsis, while p38 MAPK expression and activity were increased in SPL as well as in T-cells. Neutralization of IL-10 by in vitro use of anti-IL-10 Mab and in the IL-10 knockout animal restored the Th1 response and caused a downregulation of p38 MAPK expression and activity after CLP. Thus, IL-10 appears to contribute to the increase in p38 MAPK activity and expression and the corresponding suppression of Th1 response seen in late sepsis.

Animals↗

PubMed1999

Proteasome participates in the alteration of signal transduction in T and B lymphocytes following trauma-hemorrhage.

Proteasomes are essential components of the cellular protein degradation machinery. They are nonlysosomal and their participation is critical for (1) the removal of short lived proteins involved in metabolic regulation and cell proliferation, (2) the control of the activities of regulators involved in gene transcription, such as nuclear factor-kappa B (NF-kappa B) and signal transducer and activator of transcription (STAT1), and (3) processing of antigenic peptides for MHC class I presentation. Trauma-hemorrhage induces profound immunosuppression which is characterized by reduced splenocyte proliferation, interleukin (IL)-2 and interferon (IFN)-gamma productive capacity, increased activation of transcription factors NF-kappa B and STAT1 in splenic T lymphocytes, reduced macrophage antigen presentation capacity and inordinate release of proinflammatory cytokines, such as IL-6 and tumor necrosis factor-alpha. Furthermore, it appears that the activity of several regulatory proteins involved in immune function is altered by trauma-hemorrhage. Since proteasomes are involved in regulation and removal of regulatory proteins, we hypothesized that trauma-hemorrhage alters proteasomal activity in splenic lymphocytes. The data showed that activities of 26s proteasome from CD3+CD4+ and CD3+CD8+ splenic T lymphocytes were enhanced following trauma-hemorrhage which was associated with increased expression of NF-kappa B and STAT1. On the other hand, trauma-hemorrhage attenuated the activity of 26s proteasome from splenic B lymphocytes which was restored upon IFN-gamma stimulation and correlated with increased expression of NF-kappa B. These studies indicate a potential role for proteasomes in the regulation of signal transduction in splenic T and B lymphocytes following trauma-hemorrhage, and also suggest them as potential therapeutic targets for attenuation of immune suppression associated with this form of injury.

Animals↗

PubMed1999

Frequency of spinocerebellar ataxia types 1,2,3,6,7 and dentatorubral pallidoluysian atrophy mutations in Korean patients with spinocerebellar ataxia.

Autosomal dominant cerebellar ataxias (ADCAs) are a heterogeneous group of disorders characterized by degenerative symptoms in the cerebellum, spinal cord, and brain stem. Six different genes have been reported to be associated with ADCA, and the length of trinucleotide repeats of these genes is correlated with the age at onset and severity of symptoms. Although there are strong hereditary effects in these disorders, most of the studies carried out in heterogeneous populations and in small groups obscure the true incidence of these diseases. We examined the frequency of six types of ADCAs in 87 unrelated Korean patients with progressive ataxia and compared the results to the frequencies in other ethnic groups. Spinocerebellar ataxia (SCA) type 2 was the most frequent hereditary ataxia (12.6%) and types 3 and 6 accounted for 4.6% and 6.9% of ataxia patients, respectively. Dentatorubral pallidoluysian atrophy was also found in three patients (3.4%). No instances of SCA types 1 or 7 were detected. These findings show the striking contrast to the white population and a difference from Japanese findings. Our results demonstrate that dentatorubral pallidoluysian atrophy should be included in the differential diagnosis of Korean patients with spinocerebellar ataxia, and that there are strong hereditary effects in patients with ADCAs.

Case-Control Studies↗

PubMed1999

Increased inducible apoptosis in CD4+ T lymphocytes during polymicrobial sepsis is mediated by Fas ligand and not endotoxin.

Recent studies suggest that increased lymphocyte apoptosis (Ao) detected in peripheral blood T cells from burn patients appears to contribute to decreased lymphocyte immunoresponsiveness. However, while it is known that sepsis induces a marked depression in the splenocyte immune response (i.e. decreased interleukin-2, interferon-gamma production and proliferation) in response to the T-cell mitogen concanavalin A (Con A), it is unknown whether this depression is associated with an increase in inducible Ao and if so, which mediators control this process. To assess this, splenocytes were harvested from mice at 24 hr (a period associated with decreased Con A response) after the onset of polymicrobial sepsis [caecal ligation and puncture (CLP)] or sham-CLP (Sham) and then stimulated with 2.5 microg Con A/ml (24 hr). Septic mouse splenocytes stimulated with Con A, while not showing a change in their phenotypic make-up, did exhibit a marked increase in the percentage of splenocyte that were Ao+ which was associated with altered cytokine release. This appears to be due to an increase in the percentage of Ao+ cells in the CD4+ CD8- population and was associated with enhanced Fas antigen expression as well as an increase in mRNA for the Fas-FasL gene family. To determine if the changes in Ao are due to either endotoxin (a product of Gram-negative bacteria seen in CLP mice) or the expression of Fas ligand (FasL; a mediator of activation-induced lymphocyte Ao), a second set of studies examining Con A-inducible Ao was performed with splenocytes harvested from septic endotoxin-tolerant C3H/HeJ and the FasL-deficient C3H/HeJ-Fasl gld mice. The results show that increased splenocyte Ao detected following CLP is due to a FasL-mediated process and not to endotoxin. Thus the inadvertent up-regulation of FasL-mediated splenocyte Ao may contribute to the depression of splenocyte immune responses seen during polymicrobial sepsis.

Animals↗

PubMed1999

Does Fas ligand or endotoxin contribute to thymic apoptosis during polymicrobial sepsis?

Recent studies have shown that with the onset of sepsis there is an increase in apoptosis (Ao) in the thymus, mediated in part by steroids, which may contribute to a loss of T-cell progenitors, thereby, reducing immune functions. However, reports also suggest that these steroid effects could be mediated by Fas ligand (FasL) and/or by endotoxin (ETX). Thus, our study was to determine: 1) if polymicrobial sepsis (cecal ligation and puncture; CLP) alters thymocyte Fas antigen/receptor (Fas+) expression and 2) if the increase in Ao in septic ETX-sensitive C3H/HeN mice is seen in thymocytes from ETX-tolerant, C3H/HeJ, or the FasL-deficient/ETX-tolerant, C3H/HeJ-FasL(gld), male mouse strains subjected to CLP or sham-CLP (Sham) 12 or 24 h before they were killed. The results of flow cytometric analysis indicated that increased %Ao+ seen in thymocytes of CLP C3H/HeN mice was associated with either no change (12 h) or a decrease in %Fas+ expression at 24 h, although the %Bcl-2+ (an antiapoptotic protein) cells was depressed at both times. Additional studies examining C3H/HeJ or C3H/HeJ-FasL(gld) mice subjected to CLP show that as with the ETX-sensitive mouse, thymocyte Fas and Bcl-2 antigen expression as well as Bcl-2/Bcl-X(L/S) mRNA levels decreased although the %Ao+ increased after CLP in both ETX-tolerant and ETX-tolerant/FasL-deficient mice. Furthermore, if ETX-tolerant/FasL-deficient CLP animals were administered the steroid receptor antagonist RU-38486 (s.c., immediately after CLP) the increase in Ao was markedly attenuated, along with restoration of the percentage of cells expressing Bcl-2 and Fas antigen as well as Bcl-2/Bcl-X(L/S) mRNA levels. Thus, we concluded that increased septic thymocyte Ao is not regulated through either Fas mediated pathway or ETX, but is a result of the release of endogenous steroids possibly acting directly or indirectly on Bcl-2 expression.

Animals↗

PubMed1999

Vaccinia virus envelope D8L protein binds to cell surface chondroitin sulfate and mediates the adsorption of intracellular mature virions to cells.

We previously showed that an envelope A27L protein of intracellular mature virions (IMV) of vaccinia virus binds to cell surface heparan sulfate during virus infection. In the present study we identified another viral envelope protein, D8L, that binds to chondroitin sulfate on cells. Soluble D8L protein interferes with the adsorption of wild-type vaccinia virions to cells, indicating a role in virus entry. To explore the interaction of cell surface glycosaminoglycans and vaccinia virus, we generated mutant viruses from a control virus, WR32-7/Ind14K (A27L(+) D8L(+)) to be defective in expression of either the A27L or the D8L gene (A27L(+) D8L(-) or A27L(-) D8L(+)) or both (A27L(-) D8L(-)). The A27L(+) D8L(+) and A27L(-) D8L(+) mutants grew well in BSC40 cells, consistent with previous observations. However, the IMV titers of A27L(+) D8L(-) and A27L(-) D8L(-) viruses in BSC40 cells were reduced, reaching only 10% of the level for the control virus. The data suggested an important role for D8L protein in WR32-7/Ind14K virus growth in cell cultures. A27L protein, on the other hand, could not complement the functions of D8L protein. The low titers of the A27L(+) D8L(-) and A27L(-) D8L(-) mutant viruses were not due to defects in the morphogenesis of IMV, and the mutant virions demonstrated a brick shape similar to that of the control virions. Furthermore, the infectivities of the A27L(+) D8L(-) and A27L(-) D8L(-) mutant virions were 6 to 10% of that of the A27L(+) D8L(+) control virus. Virion binding assays revealed that A27L(+) D8L(-) and A27L(-) D8L(-) mutant virions bound less well to BSC40 cells, indicating that binding of viral D8L protein to cell surface chondroitin sulfate could be important for vaccinia virus entry.

Animals↗

PubMed1999

Cancer and cardiac mortality among 15-year survivors of cancer diagnosed during childhood or adolescence.

PURPOSE: To evaluate the impact of cardiac disease and second malignant neoplasms on late mortality rate and to identify risk factors for late mortality among 15-year survivors of cancer diagnosed during childhood or adolescence. PATIENTS AND METHODS: Gender-specific all-cause and cause-specific (cardiac disease, cancer) standardized mortality ratios were calculated. Kaplan-Meier survival estimates and Cox regression analyses were performed to determine the relationship of several demographic and treatment variables to survival. RESULTS: Patients who survived for 15 years after diagnosis had excess subsequent all-cause, cancer (second malignant neoplasms only), and cardiac mortality rates. No decrease in the late mortality rate by treatment era (1960 to 1970, 1971 to 1984) was identified. Risk factors for males included disease recurrence during the first 15 years after diagnosis, treatment with doxorubicin, and the diagnosis of Hodgkin's disease. Those for females included treatment with radiation therapy, treatment with an alkylating agent, and disease recurrence during the first 15 years after diagnosis. Cox regression analysis demonstrated that only an initial duration of remission of less than 15 years (P <.01) and treatment with doxorubicin (P =.08) were significantly associated with shorter survival time for males. No variable was significantly associated with shorter survival time for females in Cox regression analysis. CONCLUSION: Fifteen-year survivors of childhood cancer have excess mortality. More effective treatments must be developed to reduce this excess risk. Fifteen-year relapse-free survivors did not have excess mortality. This group will require continued observation to determine whether excess mortality will become apparent as more events occur.

Adolescent↗

PubMed1999

What is the role of interleukin 10 in polymicrobial sepsis: anti-inflammatory agent or immunosuppressant?

BACKGROUND: Controversy exists concerning the role of interleukin 10 (IL-10) in sepsis. When IL-10 is used in models of endotoxemia, it appears to protect (by anti-inflammatory effects), whereas in models of polymicrobial sepsis it seems to be deleterious (by immunosuppression?). However, little direct evidence for such an immunosuppressive role is available for polymicrobial sepsis. Thus the aim of this study was to determine whether IL-10 contributes to lymphocyte immunosuppression in a model of cecal ligation and puncture (CLP) and whether neutralization of IL-10 has any salutary effects on survival after sepsis. METHODS: To assess the former, polymicrobial sepsis was induced in male C57BL/6J wild-type (+/+) and C57BL/6J-IL-10 knockout(-/-) mice by CLP. Splenocytes were harvested 24 hours later and stimulated with concanavalin A to assess their proliferative capacity and their ability to release the Th1 lymphokines interleukin 2 and interferon gamma (by enzyme-linked immunosorbent assay, nanograms/millilter). To further verify the immunosuppressive role of IL-10, splenocytes were obtained from male C3H/HeN mice 24 hours after CLP and then stimulated in the presence or absence of anti-IL-10 monoclonal antibody (Mab, 4 micrograms/mL). To assess the in vivo effects of IL-10 neutralization on survival after CLP, C3H/HeN mice (16 per group) were given 250 micrograms of anti-IL-10 Mab (intraperitoneally) either immediately after CLP (before the initiation of the hyperdynamic phase) or 12 hours after CLP (the beginning of the hypodynamic state). Control mice were given nonspecific rat immunoglobulin G. RESULTS: These data indicate that IL-10 deficiency (-/-) prevents the depression of the proliferative capacity and Th1 lymphokine production after sepsis. Analysis of the interleukin 2-interferon gamma production patterns and proliferative capacity in lymphocytes treated with anti-IL-10 Mab confirmed the role of IL-10 in suppressing lymphocyte responsiveness in CLP. Interestingly, however, only delayed administration (12 hours after CLP) of anti-IL-10 markedly increased survival of mice (Fisher's exact test, P < .05). CONCLUSION: The results not only illustrate IL-10's role in septic immune dysfunction but document that anti-IL-10 administration beyond the initial proinflammatory hyperdynamic state of polymicrobial sepsis improves survival of animals subjected to sepsis.

Animals↗

PubMed1998

Is Fas ligand or endotoxin responsible for mucosal lymphocyte apoptosis in sepsis?

BACKGROUND: Apoptosis (Ao) is a normal constitutive process that seems to have pathological effects in diseases of immune deficiency and autoimmune disorders, as well as in certain lymphoid tissues during sepsis. Little is known about this process in mucosal lymphoid tissue, such as intestinal intraepithelial lymphocytes (IELs). OBJECTIVES: To determine whether sepsis induces increased Ao in small intestinal IEL, whether this was associated with functional changes in cytokine gene expression in the IEL, and which mediators control this process and their impact on the survival of the mouse with sepsis. DESIGN: Male C3H/HeN (endotoxin-sensitive), C3H/HeJ (endotoxin-tolerant), and C3H/HeJ-FasLgld (endotoxin-tolerant/Fas ligand [FasL]-deficient) mice were subjected to sepsis (cecal ligation and puncture [CLP]) and IELs were harvested at 4 (early) or 24 hours (late sepsis). Alterations in the cell phenotype and Ao (TUNEL [terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling] assay) were determined by 3-color flow cytometry. Cytokine gene expression was assessed by multiprobe RNase protection assay. RESULTS: At 4 hours after CLP, only the frequency of IEL which was CD8+ decreased markedly. By 24 hours after CLP, the number of CD8+ and CD4+ cells decreased while the proportion of double-negative cells showed a marked increase when compared with sham-controls. The percentage of Ao positive in CD8+ and CD4+ double-positive and double-negative cells increased markedly 24 hours after CLP concomitant with a significant (P<.05 vs sham-controls, Mann-Whitney U test) increase in expression of the IL-2, IL-10, and IL-15 gene. These data collectively suggest that sepsis causes lymphocyte activation-induced Ao that may be mediated by FasL. Additional studies were done to determine if the increased Ao was due to either endotoxin or FasL. The results of studies with endotoxin-tolerant C3H/HeJ or FasL-deficient C3H/HeJ-FasLgld mice showed an increase in A,, in CD4+ and CD8+ cells from septic C3H/HeJ but not C3H/HeJ-FasLgld mice. With regard to septic mortality, our results indicated that there was a marked reduction in mortality in C3H/HeJ-FasLgld vs C3H/HeJ mice. CONCLUSIONS: We conclude that the phenotypic changes associated with increased Ao may be a reflection of localized immune cell activation due to a FasL-mediated process and not endotoxin. Thus, FasL directly and/or indirectly contributes to higher septic mortality.

Animals↗

PubMed1998

Sepsis induces increased apoptosis in lamina propria mononuclear cells which is associated with altered cytokine gene expression.

Studies indicate that lymphoid tissue (e.g., thymus, bone marrow, and Peyer's patches) shows evidence of increase apoptosis (Ao, a form of nonnecrotic cell death) during sepsis. However, it is not known if mucosal lymphoid tissue, such as lamina propria (LP), also shows evidence of increased Ao and if so, is this associated with functional changes, i.e., cytokine gene expression in the LP. To examine this, male C3H/HeN mice were subjected to cecal ligation and puncture (CLP) and lamina propria mononuclear cells (LPMC) were harvested at 4 h (early sepsis) or 24 h (late sepsis). Alterations in the cell phenotype as well as Ao (Tunel assay) were determined by three-color flow cytometry. Cytokine gene expression was assessed by multiprobe RNase protection assay. Sham LPMC preparations were found to be 34.4 +/- 2.4% B220(+) (B-cells), while 12.4 +/- 2.1% were CD8(+) (cytotoxic T-cells), 22.0 +/- 0.8% were CD4(+) (helper T-cells), and 6.4 +/- 0.7% were F4/80(+) (macrophages). The frequency of B220(+) (9%* upward arrow) and CD8 (6%* upward arrow) populations increased markedly at 4 h after CLP; however, this increase was not seen at 24 h. The percentage of Ao+ in CD8(+), B220(+), and F4/80(+) cells increased markedly at both 4 and 24 h. CD4(+) cells showed a marked increase in Ao only at 24 h after CLP. When LPMC mRNA expression was examined, a significant increase in IL-2, -10, and -15 gene expression was observed only at 24 h but not 4 h after CLP. Thus, the early phenotypic changes associated with increased Ao may be a reflection of localized immune cell activation in early sepsis contributing to the increased cytokine gene expression seen in late sepsis. This localized activation may contribute to gastrointestinal inflammation and/or immune dysfunction in sepsis.

Animals↗

PubMed1998

Cell surface proteoglycans are necessary for A27L protein-mediated cell fusion: identification of the N-terminal region of A27L protein as the glycosaminoglycan-binding domain.

We previously showed that vaccinia virus infection of BSC40 cells was blocked by soluble heparin, suggesting that cell surface heparan sulfate mediates vaccinia virus binding (C.-S. Chung, J.-C. Hsiao, Y. -S. Chang, and W. Chang, J. Virol. 72:1577-1585, 1998). In this study, we extended our previous work and demonstrated that soluble A27L protein bound to heparan sulfate on cells and interfered with vaccinia virus infection at a postbinding step. In addition, we investigated the structure of A27L protein that provides for its binding to heparan sulfate on cells. A mutant of A27L protein, named D-A27L, devoid of a cluster of 12 amino acids rich in basic residues, was constructed. In contrast to the soluble A27L protein, purified D-A27L protein was inactive in all of our assays, including binding to heparin in vitro, binding to heparan sulfate on cells, and the ability to block virus infection. These data demonstrated that the N-terminal region acts as a glycosaminoglycan (GAG)-binding domain critical for A27L protein binding to cells. Previously A27L protein was thought to be involved in fusion of virus-infected cells induced by acid treatment. When we investigated whether cell surface GAGs also participate in A27L-dependent fusion, our results indicated that soluble A27L protein blocked cell fusion, whereas D-A27L protein did not. Taken together, the results therefore demonstrated that A27L-mediated cell fusion is triggered by its interaction with cell surface GAGs through the N-terminal domain.

Amino Acid Sequence↗

PubMed1998

A27L protein mediates vaccinia virus interaction with cell surface heparan sulfate.

Vaccinia virus has a wide host range and infects mammalian cells of many different species. This suggests that the cell surface receptors for vaccinia virus are ubiquitously expressed and highly conserved. Alternatively, different receptors are used for vaccinia virus infection of different cell types. Here we report that vaccinia virus binds to heparan sulfate, a glycosaminoglycan (GAG) side chain of cell surface proteoglycans, during virus infection. Soluble heparin specifically inhibits vaccinia virus binding to cells, whereas other GAGs such as condroitin sulfate or dermantan sulfate have no effect. Heparin also blocks infections by cowpox virus, rabbitpox virus, myxoma virus, and Shope fibroma virus, suggesting that cell surface heparan sulfate could be a general mediator of the entry of poxviruses. The biochemical nature of the heparin-blocking effect was investigated. Heparin analogs that have acetyl groups instead of sulfate groups also abolish the inhibitory effect, suggesting that the negative charges on GAGs are important for virus infection. Furthermore, BSC40 cells treated with sodium chlorate to produce undersulfated GAGs are more refractory to vaccinia virus infection. Taken together, the data support the notion that cell surface heparan sulfate is important for vaccinia virus infection. Using heparin-Sepharose beads, we showed that vaccinia virus virions bind to heparin in vitro. In addition, we demonstrated that the recombinant A27L gene product binds to the heparin beads in vitro. This recombinant protein was further shown to bind to cells, and such interaction could be specifically inhibited by soluble heparin. All the data together indicated that A27L protein could be an attachment protein that mediates vaccinia virus binding to cell surface heparan sulfate during viral infection.

Carrier Proteins↗

PubMed1998

Acute occlusion of the middle cerebral artery: early evaluation with triphasic helical CT--preliminary results.

PURPOSE: To evaluate use of triphasic helical computed tomography (CT) for early diagnosis of occlusion and assessment of ischemia in cases of acute middle cerebral arterial occlusion. MATERIALS AND METHODS: Thirty-five patients with acute ischemia underwent triphasic helical CT within 6 hours after symptom onset. Early arterial, perfusion, and delayed phase CT scans were obtained 18, 30, and 80 seconds, respectively, after contrast material administration. Eighteen patients had proximal middle cerebral arterial occlusion diagnosed at magnetic resonance (MR) or digital subtraction angiography. Follow-up CT or MR imaging was performed in all patients. Two independent observers interpreted images for signs of arterial occlusion, collateral vessels, and the ischemic zone. RESULTS: One observer found at least one of three signs in 17 of the 18 patients with occlusion, and the other found at least one sign in all 18: Early decreased arterial contrast enhancement was seen by both observers in 11 patients (kappa = 0.77), a nonenhancing arterial segment was seen by the two observers in 12 and 14 (kappa = 0.73), and delayed asymmetric arterial enhancement was seen in 13 and 16 (kappa = 0.49). Triphasic CT findings of the ischemic zone were consistent with follow-up CT or MR imaging findings in seven of 12 patients. CONCLUSION: Triphasic helical CT is useful for early diagnosis of acute proximal middle cerebral arterial occlusion and assessment of the ischemic zone.

Acute Disease↗

PubMed1998

Relation of plasma homocyst(e)ine to cerebral infarction and cerebral atherosclerosis.

BACKGROUND AND PURPOSE: A number of investigations support the theory that the elevated plasma homocyst(e)ine is associated with occlusive vascular disease. The aim of this study is to examine whether moderate hyperhomocyst(e)inemia is an independent risk factor for cerebral infarction. In addition, we examined the association between plasma homocyst(e)ine and the severity of cerebral atherosclerosis. METHODS: We conducted a hospital-based case-control study with 140 male controls and 78 male patients with nonfatal cerebral infarction, aged between 39 and 82 years. Plasma homocyst(e)ine levels were analyzed in 218 subjects. Fifty-five patients were evaluated for cerebral vascular stenosis by MR angiography. RESULTS: The mean plasma level of homocyst(e)ine was higher in cases than in controls (11.8+/-5.6 versus 9.6+/-4.1 micromol/L; P=0.002). The proportion of subjects with moderate hyperhomocyst(e)inemia was significantly higher in cases than in controls (16.7% versus 5.0%; P=0.004). Based on the logistic regression model, the odds ratio of the highest 5% of homocyst(e)ine levels in control group was 4.17 (95% confidence interval, 3.71 to 4. 71)(P=0.0001). After additional adjustment for total cholesterol, hypertension, smoking, diabetes, and age, the odds ratio was 1.70 (95% confidence interval, 1.48 to 1.95) (P=0.0001). The plasma homocyst(e)ine levels of patients having vessels with 3 or 2 stenosed sites were significantly higher than those of patients having vessels with 1 stenosed site or normal vessels (14.6+/-1.4, 11.0+/-1.4 versus 7.8+/-1.5, 8.9+/-1.4 micromol/L respectively; P<0. 02). Multiple logistic regression analysis revealed that moderate hyperhomocyst(e)ienemia was significantly associated with the number of stenosed vessels (P=0.001). CONCLUSIONS: These findings suggest that moderate hyperhomocyst(e)inemia is an independent risk factor for cerebral infarction and may predict the severity of cerebral atherosclerosis in patients with cerebral infarction.

Adult↗

PubMed1997

Apoptosis and host restriction of vaccinia virus in RK13 cells.

Poxviruses express a number of host range (hr) genes that control virus growth in distinctive cell types. Inactivation of hr gene expression in several reported cases has led to apoptosis of virus-infected cells. In RK13 cells, the K1L gene serves as a hr gene for vaccinia virus. We therefore investigated the effect of K1L expression in apoptosis of RK13 cells. In contrast to other hr genes, no significant increase of apoptosis was detected in RK13 cells infected with a K1L- mutant virus. Also, expression of a CHO hr gene CP77 rescues K1L- mutant virus in RK13 cells with little effect on apoptosis. We then set out an experimental approach to investigate the relationship between apoptosis and host restriction in CHO and RK13 cells. A recombinant vaccinia virus expressing a human bcl-2 gene, bcl2-VV, was constructed. Expression of bcl-2 suppressed apoptosis of virus-infected CHO cells as expected. However, bcl-2 expression did not allow virus growth in CHO cells, suggesting apoptosis suppression is not sufficient to rescue host restriction. Moreover, infection of bcl-2VV in RK13 cells induced significant apoptosis with no reduction on virus production, indicating that apoptosis does not contribute to host restriction. In consideration of this data, we conclude that host restriction of vaccinia virus in CHO and RK13 cells is mediated by a pathway distinct from apoptosis.

Animals↗

PubMed1997

Gastroesophageal reflux, motility disorders, and psychological profiles in the etiology of globus pharyngis.

The aim of this study was to investigate the origin of globus pharyngis with particular reference to esophageal disorders such as gastroesophageal reflux disease (GERD), motility disorders, structural abnormalities, other gastrointestinal tract diseases, and psychological profile. Previous studies on this subject using 24-hour pH monitoring give conflicting results and are hampered by the high background prevalence of asymptomatic GERD in the normal Western population. The local Chinese population is known to have a very low background level of GERD and therefore is an ideal study population. Twenty-six patients with globus pharyngis underwent 24-hour ambulatory pH monitoring, esophageal manometry, and esophagogastroduodenoscopy with lower esophageal biopsy. A control group of 20 patients presenting with non-ulcer dyspepsia was similarly investigated. Personality profiles of the globus pharyngis subjects and an appropriate control group were assessed. Eight of the globus pharyngis group (30.7%) had evidence of GERD, whereas only one of the controls (5%) demonstrated GERD on 24-hour esophageal pH monitoring (P < 0.05). The manometric and personality profile studies did not show significant differences between study and control groups. We concluded that the finding of GERD in patients with globus pharyngis is not a coincidental finding but that there is a true association between GERD and globus pharyngis.

Adult↗