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Biomedical subjects

H Y Hsu

Publications and source records attributed to H Y Hsu.

At least 37 records · Page 2Linked to original sources

Decreased diversity of hepatitis C virus quasispecies during bone marrow transplantation.

To elucidate the role of host immune status in the evolution and complexity of hepatitis C virus (HCV) quasispecies, three chronic HCV-infected patients who underwent bone marrow transplantation (BMT) were studied. The three transplanted patients' sera were sampled at pre-BMT, 3 months after BMT, and 12 months after BMT and the nucleotide diversity and substitution of the hypervariable region (HVR) of HCV quasispecies were analyzed. The nucleotide diversity was high at the pre-BMT period (28.2-43.4 x 10(-2) nucleotide difference/site). HVR of HCV quasispecies then became homogeneous in the first 3 months after BMT (0.11-6.40 x 10(-2) nucleotide difference/site). The nucleotide diversity of HVR at 12 months after BMT of all three patients was higher than that of 3 months after BMT but still lower than that of pre-BMT (2.09-6.40 x 10(-2) nucleotide difference/site). The analysis on nucleotide substitution rate showed a higher value between pre-BMT and 3 months after BMT (0.624-0.708 nucleotide difference/site per year) than that between 3 months and 12 months after BMT (0.072-0.127 nucleotide difference/site per year). HCV RNA titer decreased when the host had a low white cell count and increased accordingly. It was concluded that the evolution of HVR of HCV quasispecies related to the immune status of the host during BMT: after immunosuppression, an initial increase of viral populations was followed by the emergence of a dominant strain while the quasispecies gradually recovered as the immunity of the host gained its competence.

Adolescent↗

Changes of hepatitis B surface antigen variants in carrier children before and after universal vaccination in Taiwan.

Mutants of a determinant of hepatitis B surface antigen (HBsAg) identified in vaccinated children pose a potential threat to long-term success of vaccination programs. We examined the mutants of a determinant (residues 110-160) of HBsAg in hepatitis B virus (HBV) DNA-positive children identified during previous serosurveys in Taipei undertaken just before (1984), 5 years after (1989), and 10 years after (1994) universal vaccination began. In HBV DNA-positive children from 3 surveys, the prevalence of a determinant mutants increased from 8 of 103 (7.8%) in 1984 to 10 of 51(19.6%) in 1989 and 9 of 32 (28.1%) in 1994 and was higher in those fully-vaccinated than unvaccinated (12/33 vs. 15/153, P =. 0003). Most amino acid changes of the variants clustered in residues 125-129 and 140-149. In all 27 children with detectable mutants, the mean age of those vaccinated was younger than those unvaccinated (4. 8 +/- 3.8 vs. 7.9 +/- 2.3 yrs, P <.05); and mutations occurred in a region with greatest local hydrophilicity (residues 140-149) more frequently in those vaccinated than in those unvaccinated (10/12 vs. 6/15, P =.0253). More mutated residues and more mutations at neutralizing epitopes, such as N146, C147, T148, and C149, were found in the 1994 survey. Vaccinated children may contract variant infections through vertical or horizontal transmission. Universal vaccination has accelerated an accumulation of HBsAg a determinant mutants with amino acid changes critical for immune escape in vaccinated children who became carriers, suggesting that new vaccination strategies should be considered.

Carrier State↗

Difference in the effects of radioprotection between aerial and root parts of Lycium chinense.

Radiation protection from bone marrow death by consecutive injections of crude extracts from different parts of Lycium chinense (LC), root (LCR) and aerial part (LCA), before whole body X-irradiation was confirmed by tests with ICR strain mice. Both extracts were effective after intraperitoneal injection of a high dose, once a day, for seven consecutive days before irradiation. Based on the studies of endogenous hematopoietic spleen colony formation (CFUs), and the postirradiation behavior of hematograms and hematocrits, it was demonstrated that the LCR protects mice more effective when given in a dose of 500 mg/kg. Enhanced CFUs was found in the irradiation range of 4-8 Gy by various treatments. Recovery of leukocyte, erythrocyte and thrombocyte counts was significantly stimulated by the extract of LCR with 500 mg/kg administration. Stimulated recovery by the extract from the LCR was also observed in hematocrit. On the contrary, the extracts of both LCA and LCR did not markedly affect recovery of leukocyte, erythrocyte, thrombocyte counts and hematocrits by 250 mg/kg administration. It could be deduced that the uncertainly radioprotective action is induced by a possible process of enhanced regeneration of the hematopoietic stem cells due to either enhanced postirradiation repair or an increased proliferation of the hematopoietic stem cells under the suitable extract administration.

Animals↗

A simple splinting method for correction of supple congenital clasped thumbs in infants.

A splint has been designed to correct the congenital clasped thumb. It is like a short opponens splint that can keep the thumb in a position of abduction and extension without limiting wrist movement. The application of the splint was easy and adjustment for fit could be made at each visit if necessary. The device has been used in 11 infant patients (17 thumbs) with congenital clasped thumb of the supple type. The functional results were excellent in 15 of 17 thumbs, and the other two were good according to the grading system of Weckesser et al. (1968).

Female↗

Long-term follow-up of duodenal ulcer in children before and after eradication of Helicobacter pylori.

BACKGROUND: Helicobacter pylori is a well-known cause of chronic antral gastritis and plays an important role in the pathogenesis of peptic ulcer disease in adults. However, because of the relatively low incidence of duodenal ulcer in childhood, few studies have been directed specifically at the relation between the treatment of H. pylori infection and duodenal ulcer in children. An evaluation in a larger patient population is necessary to draw a conclusion. METHODS: Twenty-six children with duodenal ulcer and H. pylori antral gastritis received triple therapy (amoxicillin, bismuth, and metronidazole) to investigate whether eradication of the organisms can promote healing and prevent relapse of the ulcers in children. Endoscopic examinations were performed before, 2 months, and 12 months after the beginning of treatment. RESULTS: H. pylori infection was eradicated in 25 (96%) of the 26 patients who underwent upper endoscopic follow-up. Clinical improvement and ulcer healing were achieved in 24 (92%) of 26 children. During a mean follow-up of nearly 2 years, the annual ulcer relapse rate was estimated to be 9%. CONCLUSIONS: Triple therapy is the treatment of choice for endoscopically proven duodenal ulcer and histologically proven H. pylori antral gastritis in children. It strongly supports a causal relation between H. pylori and duodenal ulcer disease in children.

Adolescent↗

Cytokine release of peripheral blood mononuclear cells in children with chronic hepatitis B virus infection.

BACKGROUND: Immune response to hepatitis B virus (HBV) antigens or mitogens in Asian children with chronic HBV infection who are mainly perinatally infected has not been studied in connection with the production of various cytokines, although these patients are considered to be less responsive to antiviral therapy. METHODS: The production of the cytokines interferon (IFN)-gamma, lymphotoxin, interleukin (IL)-4, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta by peripheral blood mononuclear cells (PBMCs) was studied in 17 hepatitis B surface antigen (HBsAg) carrier children with raised alanine transferase levels (group 1), 17 HBsAg carrier children with normal alanine transferase levels (group 2), and 20 healthy noncarrier control subjects (group 3). RESULTS: Hepatitis B core antigen (HBcAg)-stimulated IFN-gamma production was significantly higher in group 1 than in groups 2 and 3, serum HBeAg cleared within 1 year in five of eight children in group 1 with stimulation indexes higher than 3, and HBcAg-induced IL-4 secretion was minimal in all groups. Interferon-gamma produced by PBMCs stimulated by purified HBsAg did not differ among the three groups. Higher lymphotoxin production by PBMCs stimulated by HBcAg was also noted in groups 1 and 2 than in group 3. Lipopolysaccharide (LPS)-stimulated TNF-alpha production by PBMCs was significantly higher in group 1 than in group 2. There was no association between HBeAg-anti-HBe status and production of various cytokines. No differences were seen in the profile of cytokines induced by HBV antigens or LPS in children of carrier mothers compared with children of HBsAg-negative mothers. CONCLUSION: Increased IFN-gamma production resulting from HBcAg-specific T-helper lymphocyte type 1 response, and increased TNF-alpha production may contribute to cell-mediated antiviral immune response in children with chronic hepatitis B. In HBV carrier children, the ability to produce the studied cytokines is related to whether an endogenous immune attempt to eliminate HBV infection emerges in the patients but is not related to the different modes of acquisition of HBV infection.

Adolescent↗

Long term immune response of universal hepatitis B vaccination in infancy: a community-based study in Taiwan.

OBJECTIVES: To evaluate the long term immunity provided by a universal hepatitis B vaccination program in infancy and the booster effect on school age children who had no protective antibody titers to hepatitis B surface antigen. METHODS: We conducted a community-based seroepidemiologic study of 1337 healthy 7-year-old children in Taiwan one decade after the implementation of a mass hepatitis B vaccination program. A booster vaccination was suggested for noncarrier children who did not have protective titers of surface antibody. Serologic responses and infection rates were compared with those of the nonboostered children. In a nonselected group of 39 volunteer noncarrier vaccinees, quantitative serologic response was determined before, 1 month after a booster vaccination and 1 year later. RESULTS: A total of 572 children (42.8%) had low concentrations of surface antibody, and 9 were hepatitis B surface antigen carriers (0.7%). Eighty-two percent of "nonprotected" vaccinees showed immunologic memory to a booster dose and developed protective antibody titers 1 month later; 60.6% maintained protective titers 1 year later. The frequency of new hepatitis B virus infection was similar for those who received a booster and those who did not as investigated by the core antibody seroconversion during 1-year follow-up. However, the risk was low, with annual incidences of <1% in both groups, and none became chronic carriers. CONCLUSION: According to these data a universal vaccination program in infancy provides adequate protection against hepatitis B virus infection for school age children and a booster vaccination is not recommended.

Child↗

Evaluation of the antioxidant activities of Erycibe obtusifolia.

Free radicals may be involved in various pathogenesis processes. Tissue damage and cellular toxicity of some chemicals mediated by oxygen free radicals can be monitored by studying the levels of lipid peroxidation in the tissues. The study reported here is to investigate the MDA concentrations in different tissues after various doses of Erycibe obtusifolia (EO) treatments. EO given at doses of 10, 20 and 30 mg/kg body weight is experimentally tested through oral administration. The antioxidant effect of EO extract is assessed by the measurements of hepatic, renal and splenic lipid peroxides (measured as malondialdehyde; MDA) after treatments. The results show no significant time-related and dose-dependent increase or decrease of MDA concentrations in the liver, kidney and spleen after EO administrations, respectively. The peak of antioxidant activities is found on the first day and the 6 hrs after treatments for liver and kidney, respectively. In contrast, the MDA concentrations in spleen after EO administrations remained above the normal values. This result suggests that a high dose of EO administration may contribute a little antioxidant activity in both liver and kidney.

Animals↗

Protamine enhances the efficiency of liposome-mediated gene transfer in a cultured human hepatoma cell line.

Protamine, used clinically as an antidote for heparin, is a small protein with high arginine content and is potent in folding DNA. Protamine and DNA can form a compact structure, protecting DNA from digestion by intracellular enzymes. Protamine may, therefore, enhance the efficiency of gene transfer. In this study, we tested the ability of protamine to improve liposome-mediated gene transfer efficiency in a human hepatoma cell line. The results of a preliminary gel retardation assay indicated that 10 micrograms was the minimal amount of protamine sulfate needed to completely bind 5 micrograms of a plasmid containing a reporter gene, green fluorescent protein (GFP). For transfection assays, protamine (0, 10, 50, 100, and 500 micrograms) was added to a DNA-liposome mixture (5 micrograms DNA and 20 micrograms of a mixed formulation of 2,3-dioleyloxy-N-[2(sperminecarboxamido)ethyl]-N, N-dimethyl-1-propanaminium trifluoroacetate and dioleoylphosphatidylethanolamine) to transfect cultured Huh7 cells. Transfected cells (those expressing GFP) were counted by using flow cytometry. The expression index (EI) was calculated as the transfection efficiency (% of transfected cells) with protamine divided by the transfection efficiency with DNA and liposome only. Our results show that protamine sulfate (in a range of 10-100, 10 micrograms being most efficient) addition to the liposome-DNA mixture significantly increases the EI, and transfection efficiency of GFP in Huh7 cells.

Animals↗

Microvascular changes in the retrobulbar optic nerve in idiopathic intracranial hypertension.

PURPOSE: To examine the microvascular changes in the retrobulbar optic nerve in idiopathic intracranial hypertension (PTC). METHODS: Both optic nerves from a 29-year-old man with a two year history of PTC were examined histologically and morphometrically. A semi-automated image analysis system and paraphenylenediamine (PPD) stain were employed to resolve sufficiently the microvascular images for counts and measurement. RESULTS: There were 150 vessels distributed in the optic nerves which revealed the following: The average lumen of the vessels in outer sectors were larger than those of the inner sector vessels (168.17 microns 2 vs. 46.99 microns 2; p = 0.0338; OD; and 251.96 microns 2 vs. 130.02 microns 2; p = 0.029; OS) while in the normal control optic nerve the outer and inner area lumens were reversed in size-differential, but this did not show a statistical difference. The thickness of the PTC optic nerve vessel walls in the outer sectors was also greater than that of the walls in the inner sectors (4.95 microns vs. 2.67 microns; p = 0.013; OD and 5.25 microns vs. 3.34 microns; p = 0.019; OS); the same measurements in the normal optic nerve showed a reversed ratio, which was opposite that of the experimental group and but not statistically different. CONCLUSION: This pattern of microvascular changes is consistent with the selective axonal loss in the peripheral area of each optic nerve as much more severe than that in the inner sectors.

Adult↗

Molecular and electrophysiological characterizations of fGluR3 alpha, an ionotropic glutamate receptor subunit of a teleost fish.

Here we report the cloning and functional analysis of a cDNA encoding a functional glutamate receptor subunit of Oreochromis sp., a freshwater teleost fish. The deduced amino acid sequence of this cDNA clone, fGluR3 alpha, displays the highest sequence identity to that of the mammalian GluR3 subunit. Results of quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis indicated that the expression level of fGluR3 alpha in the cerebellum was much less than that in the telencephalon and optical lobe. Similar to its mammalian counterpart, variants of fGluR3 alpha were created by alternative splicing and RNA editing at the R/G site. The channel properties of homomeric fGluR3 alpha expressed in Xenopus oocytes were similar to those of the mammalian alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-preferring receptors. The rank order of agonist potency of the expressed fGluR3 alpha is AMPA > or = glutamate > or = quisqualate > domoate > or = kainate. This is the first functional glutamate receptor of teleost fish being demonstrated to be sensitive to AMPA. Furthermore, this study suggested a strong functional conservation of AMPA-preferring receptors in vertebrates.

Amino Acid Sequence↗

Ligand binding to macrophage scavenger receptor-A induces urokinase-type plasminogen activator expression by a protein kinase-dependent signaling pathway.

Macrophage scavenger receptor-type A (MSR-A) has been implicated in the transmission of cell signals and the regulation of diverse cellular functions (Falcone, D. J., and Ferenc, M. J. (1988) J. Cell. Physiol. 135, 387-396; Falcone, D. J., McCaffrey, T. A., and Vergilio, J. A. (1991) J. Biol. Chem. 266, 22726-22732; Palkama, T. (1991) Immunology 74, 432-438; Krieger, M., and Herz, J. (1994) Annu. Rev. Biochem. 63, 601-637); however, the signaling mechanisms are unknown. In studies reported here, we demonstrate that binding of both lipoprotein and non-lipoprotein ligands to MSR-A induced protein tyrosine phosphorylation and increased protein kinase C (PKC) activity leading to up-regulated urokinase-type plasminogen activator (uPA) expression. Specifically, the binding of acetylated low density lipoprotein and fucoidan to MSR-A in human THP-1 macrophages triggered tyrosine phosphorylation of many proteins including phospholipase C-gamma1 and phosphatidylinositol-3-OH kinase. Inhibitors of tyrosine kinase dramatically reduced MSR-induced protein tyrosine phosphorylation and PKC activity. Moreover, inhibitors of tyrosine kinase and PKC reduced uPA activity expressed by THP-1 macrophages exposed to MSR-A ligands. The intracellular signaling response for tyrosine phosphorylation following ligand binding was further demonstrated by using the stable MSR-transfected Bowes cells that express surface MSR-A. These findings establish for the first time a signaling pathway induced by ligand binding to MSR-A and suggest a molecular model for the regulation of macrophage uPA expression by specific ligands of the MSR-A.

Cell Line↗

A histopathologic and morphometric differentiation of nerves in optic nerve hypoplasia and Leber hereditary optic neuropathy.

OBJECTIVES: To characterize and quantitate optic nerve histopathologic and morphometric differences between optic nerve hypoplasia (ONH) as an early and congenital form of intrinsic axonal loss and Leber hereditary optic neuropathy (LHON) as a late and acquired form of intrinsic axonal loss. MATERIALS AND METHODS: Optic nerves from 3 sources were examined: a 42-year-old healthy woman (control), a 53-year-old woman with ONH diagnosed postmortem, and a 74-year-old woman with LHON. The optic nerves were processed, embedded, and stained with a 1% solution of paraphenylene diamine. Histopathologic and morphometric analyses were performed via light microscopy and a semiautomatic computer image analysis system. RESULTS: The ONH showed severe axonal depletion without degenerated profiles in an inferonasal sector, with only a small superotemporal sector having a near normal appearance. The LHON revealed general axonal depletion centrally, fibrocytic scarring, scattered "degeneration dust," and evidence of minimal inflammation, with residual axons limited to superior and temporal peripheral clusters. Morphometric analysis revealed total fiber populations of 98,000 in the ONH optic nerve and 48,000 in the LHON optic nerve, representing 90% and 95% reductions, respectively, compared with the control optic nerve (1.2 million fibers). CONCLUSIONS: Optic nerve hypoplasia and LHON present 2 distinguishable and distinctive patterns of nerve fiber distribution and axonal dropout. The lack of degenerated axons in ONH indicates that any axonal death probably occurred through apoptosis during development. In LHON, degenerated axons and minimal grade of inflammation were obvious, implicating a more "active" pathologic process. This study describes distinctions between these 2 optic neuropathies.

Adult↗

Long-term effects of sensory reeducation following digital replantation and revascularization.

The long-term maintenance of sensory gain following sensory reeducation is still unknown for replanted digits. Ten patients with 18 replanted or revascularized digits, who had received a formal sensory reeducation program for 1.5 years postoperatively, were reevaluated with moving two-point discrimination and Semmes-Weinstein pressure threshold test after discontinuing sensory reeducation for 1 year. Another four patients with seven replanted or revascularized digits, who have never received sensory reeducation after surgery, were also followed up in the same way. After cessation of sensory reeducation, the degree of moving two-point discrimination became significantly worse in the formal sensory-reeducated group (P < 0.05) and significantly improved in the group without sensory reeducation initially (P < 0.05), whereas it showed a nonsignificant change of Semmes-Weinstein threshold both in the group with formal sensory reeducation and without sensory reeducation. Sensory retraining did influence the progressive change of moving two-point discrimination, but not in a parallel way with the Semmes-Weinstein threshold test.

Adult↗

Hepatitis B surface antigenemia at birth: a long-term follow-up study.

OBJECTIVE: To investigate the prevalence and outcome of hepatitis B surface antigenemia in newborns of hepatitis B e antigen (HBeAg)-positive hepatitis B surface antigen (HBsAg) carrier mothers under the current immunoprophylaxis program. STUDY DESIGN: From 1984 to 1993, 665 high-risk newborns born to HBeAg-positive HBsAg carrier mothers were prospectively recruited. The newborns were tested for HBsAg soon after birth, before hepatitis B immune globulin administration. All newborns received hepatitis B immune globulin within 24 hours after birth plus subsequent hepatitis B vaccination. Those who were seropositive for HBsAg at birth were regularly followed up for their hepatitis B virus (HBV) markers, liver function profiles, and alpha-fetoprotein levels from 1984 to 1996. RESULTS: Sixteen (2.4%) of the 665 subjects were found to be seropositive for HBsAg at birth, and all remained HBsAg-positive at 6 months of age. Twelve of the 16 received long-term follow-up care, and all were confirmed to have chronic HBV infection. Of the 12, 2 had HBeAg seroconversion, and 1 had alanine aminotransferase flares without HBeAg seroconversion. Delayed appearance of hepatitis B core antibody (anti-HBc) occurred in 2 without alanine aminotransferase elevation. CONCLUSIONS: Current immunoprophylaxis strategy does not protect newborns with surface antigenemia, apparently acquired in utero, from becoming HBV carriers. Immunologic attempts to eliminate HBV may occur in carrier children infected in utero, despite their profound immune tolerance to HBV.

Alanine Transaminase↗

Antibodies to E2 protein of hepatitis G virus in children: different responses according to age at infection.

OBJECTIVES: To study viral persistence and antibody responses after hepatitis G virus (HGV) infection in children of various ages. STUDY DESIGN: We performed an enzyme immunoassay for antibodies to E2 protein (anti-E2) of HGV and reverse-transcription polymerase chain reaction assay for HGV RNA on serum samples. RESULTS: Of 28 infants born to HGV RNA-positive mothers, 17 were found to be positive for HGV RNA. None were positive for anti-E2. All 17 infected infants continued to have viremia except 1 who converted to HGV RNA-negative status at 24 months. Six infants had mild elevations of alanine aminotransferase levels (5 HGV-positive and 1 HGV-negative). An additional 14 HGV-infected children (aged 6 months to 14 years) with posttransfusion HGV infection were tested for anti-E2 3 months and 12 months after blood transfusion. None of the HGV RNA-positive serum samples were positive for anti-E2; however, 4 of the 8 children with resolving HGV infection were positive for anti-E2 1 year later. CONCLUSIONS: Mother-to-infant transmission of HGV resulted in a high viral persistence rate and lack of immune responses to HGV. In contrast, anti-E2 appeared in children who recovered from posttransfusion HGV infection. Mode of transmission and age at infection may be important factors in determining persistent HGV infection and defective immune response to HGV.

Adenovirus E2 Proteins↗

Precore stop codon mutant in chronic hepatitis B virus infection in children: its relation to hepatitis B e seroconversion and maternal hepatitis B surface antigen.

BACKGROUND/AIMS: The aims of this study were to investigate the significance of the precore stop codon mutant in the natural course of hepatitis B virus infection in children, and the influence of maternal transmission. METHODS: Sequential sera from 80 hepatitis B virus carrier children both before and after e seroconversion during long-term follow-up were studied using the polymerase chain reaction-amplification created restriction site method. Direct sequencing of the precore region was performed in 89 sera from 32 of the 80 children. RESULTS: The precore stop codon mutant coexisting with wild strain was found in 10% of children initially, and later in 25% of children before e seroconversion. After e seroconversion, wild type was still present in 75% and mutant in 39% of children at the end of follow-up. The mutant alone was present in 15% of anti-HBe positive children without concomitant aminotransferase elevation. Children with earlier emergence of this mutant tended to have higher peak aminotransferase levels. This mutant emerged less frequently in children of hepatitis B virus carrier mothers (37.5%) than in those of non-carrier mothers (65%) (p<0.05). CONCLUSIONS: These observations suggest that this mutant is selected by host immune pressure, but is not an initiator in the loss of immune tolerance during childhood chronic hepatitis B virus infection.

Adolescent↗

The motion analysis system and goniometry of the finger joints.

The application of a video-based motion analysis system for goniometry of finger joints during measurement of the fingertip motion area has been assessed. The results indicate that the motion analysis system is reliable for angular measurements of finger joints that are comparable with those obtained by conventional goniometer. The advantages of using the motion analysis system is that it can record and show the changes in angle of all finger joints continuously during finger motion.

Adolescent↗