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Biomedical subjects

S S Han

Publications and source records attributed to S S Han.

At least 19 recordsLinked to original sources

Nucleotide sequence and taxonomy of Cycas necrotic stunt virus. Brief report.

Cycas necrotic stunt virus (CNSV) is the only well-characterized virus from gymnosperm. cDNA segments corresponding to the bipartite genome RNAs (RNA1, RNA2) were synthesized and sequenced. Each RNA encoded a single polyprotein, flanked by the 5' and 3' non-coding regions (NCR) and followed by a poly (A) tail. The putative polyproteins encoded by RNA1 and RNA2 had sets of motifs, which were characteristic of viruses in the genus Nepovirus. The polyproteins showed higher sequence identities to Artichoke Italian latent virus, Grapevine chrome mosaic virus and Tomato black ring virus, all of which belong to subgroup b of the genus Nepovirus, than to other nepoviruses. Phylogenetic analysis of RNA dependent RNA polymerase and coat protein also showed closer relationships with these viruses than other viruses. The data obtained supported the taxonomical status of CNSV as a definitive member of the genus Nepovirus, subgroup b.

3' Untranslated Regions↗

Nucleotide sequence of a Japanese isolate of Squash mosaic virus. Brief report.

The complete nucleotide sequence of the RNA-1 of Squash mosaic virus (SqMV) was determined using a Japanese isolate (Y-SqMV). The sequence consisted of 5865 nucleotides excluding the poly (A) at the 3' terminus and contained a single long open reading frame with a coding capacity for a protein of Mr209971. Analysis of the deduced amino acid sequence suggested a genomic organization typical of comoviruses. The nucleotide sequence of the RNA-2 of Y-SqMV was also determined and compared with the SqMV isolates from the United States. The larger and smaller capsid protein (CP) coding region was compared to those of K-SqMV and Z-SqMV, which represent two subgroups of SqMV. The larger CP gene of Y-SqMV showed 93.0% and 88.0% identities with those of K-SqMV and Z-SqMV, respectively at the nucleotide level. The smaller CP gene of Y-SqMV was 94.1% and 88.4% identical with those of K-SqMV and Z-SqMV. The results suggested that the Japanese SqMV isolate (Y-SqMV) is distinct from those in the United States, and might represent a third subgroup.

Comovirus↗

Evaluation of developmental toxicity in rats exposed to the environmental estrogen bisphenol A during pregnancy.

Bisphenol A (BPA) is an essential component of epoxy resins used in the lacquer lining of metal food cans, as a component of polycarbonates, and in dental sealants. The present study was conducted in an attempt to evaluate the adverse effects of the environmental estrogen BPA on initiation and maintenance of pregnancy and embryofetal development after maternal exposure during the entire period of pregnancy in Sprague-Dawley rats. The test chemical was administered by gavage to mated females from days 1 to 20 of gestation (sperm in varginal lavage = day 0) at dose levels of 0, 100, 300, and 1000 mg/kg. All females were subjected to caesarean section on day 21 of gestation and their fetuses were examined for external, visceral and skeletal abnormalities. In the 1000 mg/kg group, significant toxic effects including abnormal clinical signs, decreased maternal body weight and body weight gain, and reduced food consumption were observed in pregnant rats. An increase in pregnancy failure was also found in the successfully mated females. In addition, increased number of embryonal deaths, increased postimplantation loss, reduced litter size and fetal body weight, and decreased number of fetal ossification centers of several skeletal districts were seen. On the contrary, no significant changes induced by BPA were detected in the number of corpora lutea and implantation sites and by fetal morphological examinations. In the 300 mg/kg group, suppressed maternal body weight and body weight gain, decreased food intake and reduced body weight of male fetuses were seen. There were no adverse signs of either maternal toxicity or developmental toxicity in the 100 mg/kg group. It was concluded that BPA administration during the entire period of pregnancy in rats produced pregnancy failure, pre- and postimplantation loss, fetal developmental delay and severe maternal toxicity, but no embryo-fetal dysmorphogenesis at an oral exposure level of 1000 mg/kg.

Air Pollutants↗

Evaluation of denaturing high performance liquid chromatography (DHPLC) for the mutational analysis of the neurofibromatosis type 1 ( NF1) gene.

The identification of mutations in the NF1 gene causing type 1 neurofibromatosis (NF1) has presented a considerable challenge because of the large size of the gene, the lack of significant mutational clustering, the diversity of the underlying pathological lesions and the presence of NF1 pseudogenes. Denaturing high performance liquid chromatography (DHPLC), a high throughput, non-hazardous and largely automated heteroduplex-based technique, is in many ways ideally suited to mutation detection in this condition. DHPLC was therefore optimised for the rapid screening of the 60 exons and splice junctions of the NF1 gene in patients with NF1. The sensitivity of DHPLC was evaluated in a retrospective study of a cohort of 111 unrelated NF1 patients with known germline mutations; 97% of mutations were detected. In a subsequent prospective analysis of 50 unrelated NF1 patients, germline mutations were identified in 34 individuals (68%), 22 of these alterations being novel. This represents the highest rate of mutation detection so far reported for the NF1 gene with a single screening technique and genomic DNA as a target.

Base Sequence↗

Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation.

A wide array of phenolic substances, particularly those present in edible and medicinal plants, have been reported to possess substantial anticarcinogenic and antimutagenic activities. The majority of naturally occurring phenolics retain antioxidative and anti-inflammatory properties which appear to contribute to their chemopreventive or chemoprotective activity. Cyclooxygenase-2 (COX-2) inducible and nitric oxide synthase (iNOS) are important enzymes that mediate inflammatory processes. Improper up-regulation of COX-2 and/or iNOS has been associated with pathophysiology of certain types of human cancers as well as inflammatory disorders. Since inflammation is closely linked to tumor promotion, substances with potent anti-inflammatory activities are anticipated to exert chemopreventive effects on carcinogenesis, particularly in the promotion stage. Examples are curcumin, a yellow pigment of turmeric (Curcuma longa L., Zingiberaceae), the green tea polyphenol epigallocatechin gallate (EGCG), and resveratrol from grapes (Vitis vinifera, Vitaceae) that strongly suppress tumor promotion. Recent studies have demonstrated that eukaryotic transcription factor nuclear factor-kappa B (NF-kappa B) is involved in regulation of COX-2 and iNOS expression. Several chemopreventive phytochemicals have been shown to inhibit COX-2 and iNOS expression by blocking improper NF-kappa B activation. Multiple lines of compelling evidence indicate that extracellular-regulated protein kinase and p38 mitogen-activated protein kinase are key elements of the intracellular signaling cascades responsible for NF-kappa B activation in response to a wide array of external stimuli. Curcumin, EGCG and resveratrol have been shown to suppress activation of NF-kappa B. One of the plausible mechanisms underlying inhibition of NF-kappa B activation by aforementioned phytochemicals involves repression of degradation of the inhibitory unit I kappa B alpha, which hampers subsequent nuclear translocation of the functionally active subunit of NF-kappa B.

Animals↗

Generation of macrophages from early T progenitors in vitro.

Early T progenitors in the thymus have been reported to have the capacity to develop into B cells, thymic dendritic cells, and NK cells. Here we describe conditions that induce early T progenitors to develop into macrophages. Initially, we observed that early T progenitors could be induced to develop into macrophages by cytokines produced from a thymic stromal cell line, TFGD, and later we found that the cytokine mixture of M-CSF plus IL-6 plus IL-7 also induced macrophage differentiation from pro-T cells. M-CSF by itself was unable to induce macrophage differentiation from early T progenitors. To correlate this observation with the developmental potential of early T progenitors, mouse embryonic thymocytes were sorted into four populations, pro-T1 to pro-T4, based on the expression of CD44 and CD25, and then cultured with TFGD culture supernatant. We found that pro-T1 and pro-T2 cells, but not pro-T3 and pro-T4 cells, generate macrophages. Limiting dilution analysis of the differentiation capability of sorted pro-T2 cells also confirmed that pro-T2 cells could generate macrophages. These results suggest that T cells and thymic macrophages could originate from a common intrathymic precursor.

Animals↗

Platelet-activating factor-induced early activation of NF-kappa B plays a crucial role for organ clearance of Candida albicans.

In this study, we have investigated the mechanisms underlying organ susceptibility to candida infection. Infection of BALB/c mice with Candida albicans led to both an early (1-8 h) and late (24-48 h) activation of NF-kappaB in the organs resistant to C. albicans, including the lung and spleen. In susceptible organs such as the kidneys, early activation of NF-kappaB was not observed. The kinetics of TNF-alpha mRNA expression paralleled those of NF-kappaB activation in all organs examined. Blocking the effects of endogenous platelet-activating factor (PAF) by pretreatment with the PAF antagonist BN50739 or antioxidants significantly reduced the early activity of NF-kappaB and TNF-alpha mRNA expression, and increased the recovery of C. albicans in the lung and spleen. Importantly, administration of PAF 5 min prior to the infection resulted in the appearance of early activities of NF-kappaB and TNF-alpha mRNA expression, followed by a nearly complete clearance of the organisms in the kidneys. Pretreatment with anti-TNF-alpha Ab resulted in an enhanced susceptibility to C. albicans, and the PAF-mediated resistance was abrogated by anti-TNF-alpha in all organs examined. These data indicated that endogenously produced PAF in response to C. albicans is a key molecule involved in the early activation of NF-kappaB, which, in turn, renders the organ resistant to the fungus by promoting the production of anti-candidal proinflammatory cytokines such as TNF-alpha. Susceptible organs, including the kidneys, lack the capacity to generate a sufficient PAF-induced early NF-kappaB response.

Adjuvants, Immunologic↗

Lead treatment in vitro at early developmental stage of bone marrow-derived macrophages enhances NO production through IL-1beta and IL-6 but not TNF-alpha.

Lead (Pb(2+)) is known to decrease or block nitric oxide (NO) production by mature macrophages (mphi). Bone marrow cells were treated with various doses of lead in vitro and the morphological and functional changes were observed. Bone marrow cells were treated with various doses of lead (1, 10, 20 and 50 microM) at the start of culture with mphi growth factor (CSF-1), and after 6-7 days of culture, the resultant mphi (bone marrow-derived mphi, BMDM) showed decreased NO production. Unexpectedly, BMDM from the lowest does of lead treatment (1.0 microM) showed increased NO production. The increased NO production was due to increased expression of the iNOS gene and concurrent enhanced transcript levels of proinflammatory cytokines such as IL-1beta and IL-6, but not TNF-alpha. Lead treatment on mature BMDM showed decreased NO production in a dose-dependent manner. These results suggest that a low dose of lead affects developmental characteristics of BMDM through different proinflammatory cytokines, and the lead effects on precursor cells of mphi and mature mphi are different.

Animals↗

Capsaicin suppresses phorbol ester-induced activation of NF-kappaB/Rel and AP-1 transcription factors in mouse epidermis.

Capsaicin, the principal pungent ingredient of hot chili peppers, has anti-inflammatory and analgesic properties and is currently used as a topical cream for the management of various neuropathic conditions. In the present study, topical application of capsaicin onto dorsal skin of female ICR mice strongly suppressed phorbol ester-stimulated activation of NF-kappaB via blockade of IkappaB-alpha degradation with subsequent inhibition of nuclear translocation of the functionally active NF-kappaB subunit, p65. Likewise, phorbol ester-induced activation of activator protein-1 (AP-1) was abolished by capsaicin pretreatment. Since altered transactivation of NF-kappaB and AP-1 has been implicated for neoplastic transformation and progression, the suppression of these transcription factors by capsaicin may account for its previously reported chemopreventive effects on mouse skin tumorigenesis as well as inflammation.

Animals↗

Metabolism of flupyrazofos in the isolated perfused rat liver.

To investigate the hepatic metabolism of the new insecticide flupyrazofos [O,O-diethyl O-(1-phenyl-3-trifluoromethylpyrazol-5-yl) phosphorothioate], isolated rat liver was perfused with flupyrazofos under single-pass conditions. In outflow perfusate and bile, 1-phenyl-3-trifluoromethyl-5-hydroxyprazole (PTMHP), PTMHP-sulfate and PTMHP-glucuronide conjugates were identified as the metabolites of flupyrazofos. However, O,O-diethyl O-(1-phenyl-3-trifluoromethylpyrazol-5-yl) phosphate (flupyrazofos oxon) was not detected. A HPLC method with UV detection was used to investigate the hepatic disposition of flupyrazofos and its metabolite PTMHP. The concentrations of flupyrazofos, PTMHP and PTMHP conjugates in outflow perfusate reached steady-state levels within 20 min after commencing perfusion of 7.3 microM flupyrazofos. At steady state, the mean extraction ratio of flupyrazofos was 0.93 (+/- 0.01) and clearance was 26.1 (+/- 0.2) ml min-1 which nearly approached perfusate flow rate (28 ml min-1). PTMHP accounted for 55.7 (+/- 5.8)% of eliminated flupyrazofos and was recovered as unchanged PTMHP, PTMHP-sulfate and PTMHP-glucuronide in the bile as well as the outflow perfusate.

Animals↗

Mode of antiviral activity of water soluble components isolated from Elfvingia applanata on vesicular stomatitis virus.

A preparation of water soluble components (EA) was made from carpophores of Elfvingia applanata (Pers.) Karst and its in vitro antiviral activity on vesicular stomatitis virus [(Indiana serotype, VSV(IND)] was investigated by plaque reduction assay. EA exhibited potent antiviral activity on VSV(IND) growth and negligible cytotoxicity on Vero cells, 50% effective concentration (EC50) of 104 microg/ml and 50% cytotoxic concentration (CC50) of 3,793 microg/ml, respectively. Selectivity index (SI, CC50/EC50) of EA on Vero cell and VSV(IND) was about 36.5. EA did not display either a direct virucidal effect on VSV(IND) or induction of antiviral substance by Vero cells upon its treatment. Thus, the mode of antiviral activity of EA was studied at steps of viral adsorption onto cell. When both EA and virus were added to cell monolayers, titer of cell-free virus in culture supernatant increased in ca. 30-40% compared with that of control group and titer of cell-associated virus was 60-100% higher than that of control group. These results suggested that antiviral activity of EA on VSV(IND) might be due to the hindrance of viral entry to cells at either endocytosis or loss of envelope.

Animals↗

Sequence diversity and interrelationships among isolates of satsuma dwarf-related viruses.

The 3'-region of RNA2 of three viruses (Natsudaidai dwarf virus (isolate ND-1), and two unidentified isolates (LB-1, Az-1)), which were related to Satsuma dwarf virus (SDV), were sequenced. Phylogenetic analysis including the previously reported SDV-related viruses (Citrus mosaic virus (CiMV, Ci-968), Navel orange infectious mottling virus (NIMV, NI-1)) showed that they were classified into three groups, SDV (S-58), CiMV (Ci-968, LB-1, Az-1, ND-1), and NIMV (NI-1). The results suggested these groups might correspond to the three distinct virus species. ND-1, LB-1, and Az-1 were considered strains of CiMV, although they do not induce citrus mosaic on the fruit rind.

3' Untranslated Regions↗

Acemannan purified from Aloe vera induces phenotypic and functional maturation of immature dendritic cells.

Acemannan, a major carbohydrate fraction of Aloe vera gel, has been known to have antiviral and antitumoral activities in vivo through activation of immune responses. The present study was set out to define the immunomodulatory activity of acemannan on dendritic cells (DCs), which are the most important accessory cells for the initiation of primary immune responses. Immature DCs were generated from mouse bone marrow (BM) cells by culturing in a medium supplemented with GM-CSF and IL-4, and then stimulated with acemannan, sulfated acemannan, and LPS, respectively. The resultant DCs were examined for phenotypic and functional properties. Phenotypic analysis for the expression of class II MHC molecules and major co-stimulatory molecules such as B7-1, B7-2, CD40 and CD54 confirmed that acemannan could induce maturation of immature DCs. Functional maturation of immature DCs was supported by increased allogeneic mixed lymphocyte reaction (MLR) and IL-12 production. The differentiation-inducing activity of acemannan was almost completely abolished by chemical sulfation. Based on these results, we propose that the adjuvant activity of acemannan is at least in part due to its capacity to promote differentiation of immature DCs.

Adjuvants, Immunologic↗

Satsuma dwarf and related viruses belong to a new lineage of plant picorna-like viruses.

Satsuma dwarf virus (SDV) and two closely related viruses, Citrus mosaic (CiMV), and Naval orange infectious mottling (NIMV), seriously affect citrus varieties grown in Japan and East Asia. All three viruses have icosahedral particles built of two proteins encapsidating two single-stranded genomic RNAs. The natural mode of transmission of these SDV-like viruses is unknown, and they were previously placed among tentative members of the family Comoviridae. Recently, a complete genome of SDV was sequenced, and its replication-related proteins were found only distantly related to those of viruses from the family Comoviridae (Iwanami T., Kondo Y., and Karasev A.V. J Gen Virol 80, 793-797, 1999). Here we present a partial genome sequence for another SDV-like virus, NIMV, and a thorough phylogenetic analysis of the gene products encoded by SDV, CiMV, and NIMV to assess their relationships with picorna-like viruses infecting plants, insects, and vertebrates. The RdRp's of SDV-like viruses form a new lineage, separate from members of Como- and Sequiviridae families. Phylogenetic analysis suggests that SDV-like viruses may represent a new family of plant picorna-like viruses. Sequence analysis of the capsid proteins (CPs) encoded by the SDV-like viruses revealed a region of similarity to CPs of animal calici- and picornaviruses that encompasses the structural core of the eight-strand beta-barrel characteristic of picornaviral CPs. These data suggest that SDV and related bipartite viruses evolved separately from the viruses in the family Comoviridae and that the split of an ancestor, monopartite picorna-like virus genome might have occurred more than once.

Amino Acid Sequence↗

Specificity of relations between children's control-related beliefs and internalizing and externalizing psychopathology.

The authors examined the specificity of the relation between 3 types of control-related beliefs and internalizing and externalizing psychopathology in a sample of 290 clinic-referred children aged 7 to 17 years. Self-reported beliefs about control (the capacity to cause an intended outcome), contingency (the degree to which a desired outcome can be controlled by a relevant behavior), and competence (an individual's ability to produce the relevant behavior) across 3 domains (academic, behavioral, and social) showed more specific relations with psychopathology than have been previously reported. Among children with externalizing psychopathology, internalizing psychopathology may be specifically associated with increased self-critical awareness about their conduct; externalizing psychopathology may attenuate the specific negative relation between internalizing psychopathology and control-related beliefs in the social domain.

Adolescent↗

Subacute toxicity of chitosan oligosaccharide in Sprague-Dawley rats.

A subacute oral toxicity study of chitosan oligosaccharide was performed in Sprague-Dawley rats of both sexes. Each 36 male and female rats were administered by gavage with 500, 1,000 and 2,000 mg/kg/day for 4 weeks (7 days/week), respectively. Examinations regarding clinical signs, body weights, hematological and biochemical parameters, and histopathological examinations were carried out. There were no significant differences in behavior or external appearance, body weight and food consumption between control and treated rats. In addition, no significant differences in urinalysis, hematology, blood biochemistry, relative organ weights and histopathological findings were found in both control and treated rats. In conclusion, it was suggested that subacute toxicity of chitosan oligosaccharide was low and the no-observed adverse effect level was considered to be over 2,000 mg/kg in rats.

Animals↗

A 10-year experience of liver transplantation for hepatitis C: analysis of factors determining outcome in over 500 patients.

OBJECTIVE: To determine the factors affecting the outcome of orthotopic liver transplantation (OLT) for end-stage liver disease caused by hepatitis C virus (HCV) and to identify models that predict patient and graft survival. SUMMARY BACKGROUND DATA: The national epidemic of HCV infection has become the leading cause of hepatic failure that requires OLT. Rapidly increasing demands for OLT and depleted donor organ pools mandate appropriate selection of patients and donors. Such selection should be guided by a better understanding of the factors that influence the outcome of OLT. METHODS: The authors conducted a retrospective review of 510 patients who underwent OLT for HCV during the past decade. Seven donor, 10 recipient, and 2 operative variables that may affect outcome were dichotomized at the median for univariate screening. Factors that achieved a probability value less than 0.2 or that were thought to be relevant were entered into a stepdown Cox proportional hazard regression model. RESULTS: Overall patient and graft survival rates at 1, 5, and 10 years were 84%, 68%, and 60% and 73%, 56%, and 49%, respectively. Overall median time to HCV recurrence was 34 months after transplantation. Neither HCV recurrence nor HCV-positive donor status significantly decreased patient and graft survival rates by Kaplan-Meier analysis. However, use of HCV-positive donors reduced the median time of recurrence to 22.9 months compared with 35.7 months after transplantation of HCV-negative livers. Stratification of patients into five subgroups, based on time of recurrence, revealed that early HCV recurrence was associated with significantly increased rates of patient death and graft loss. Donor, recipient, and operative variables that may affect OLT outcome were analyzed. On univariate analysis, recipient age, serum creatinine, donor length of hospital stay, donor female gender, United Network for Organ Sharing (UNOS) status of recipient, and presence of hepatocellular cancer affected the outcome of OLT. Elevation of pretransplant HCV RNA was associated with an increased risk of graft loss. Of 15 variables considered by multivariate Cox regression analysis, recipient age, UNOS status, donor gender, and log creatinine were simultaneous significant predictors for patient survival. Simultaneously significant factors for graft failure included log creatinine, log alanine transaminase, log aspartate transaminase, UNOS status, donor gender, and warm ischemia time. These variables were therefore entered into prognostic models for patient and graft survival. CONCLUSION: The earlier the recurrence of HCV, the greater the impact on patient and graft survival. The use of HCV-positive donors may accelerate HCV recurrence, and they should be used judiciously. Patient survival at the time of transplantation is predicted by donor gender, UNOS status, serum creatinine, and recipient age. Graft survival is affected by donor gender, warm ischemia time, and pretransplant patient condition. The authors' current survival prognostic models require further multicenter validation.

Adult↗

Dyspnea and palpitation during pregnancy.

OBJECTIVES: Dyspnea and palpitation are common features of pregnancy. While several theories have been put forward to explain the etiology of gestational dyspnea and palpitation, there have been few systemic studies of its incidence, severity and time-course in a group of normal women. METHODS: We interviewed postpartum women, within 3 days after delivery, about dyspnea and palpitation. Separately from this interview, we performed 24-hour ECG monitoring for obstetric patients with palpitation before delivery. RESULTS: The subjects interviewed were 261 women, of whom 37.5 percent and 11.5 percent experienced dyspnea and palpitation, respectively. These symptoms had tendency to increase to term. The presence of arrhythmias could be documented in only 22% of patients having 24-hour Holter monitoring. CONCLUSION: Dyspnea and palpitation were common among normal pregnant women and had a tendency to increase to term.

Adult↗