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Biomedical subjects

C Y Lu

Publications and source records attributed to C Y Lu.

At least 55 records · Page 3Linked to original sources

Oxidative damage elicited by imbalance of free radical scavenging enzymes is associated with large-scale mtDNA deletions in aging human skin.

Mitochondrial DNA (mtDNA) mutations and impaired respiratory function have been demonstrated in various tissues of aged individuals. We hypothesized that age-dependent increase of ROS and free radicals production in mitochondria is associated with the accumulation of large-scale mtDNA deletions. In this study, we first confirmed that the proportion of mtDNA with the 4977 bp deletion in human skin tissues increases with age. We then investigated the 8-hydroxy-2'-deoxyguanosine (8-OH-dG) content in skin tissues and lipid peroxides content of the skin fibroblasts from subjects of different ages. The results showed an age-dependent increase of 8-OH-dG level in the total DNA of skin tissues of the subjects above the age of 60 years. The specific content of malondialdehyde, an end product of lipid peroxidation, was also found to increase with age. On the other hand, we examined the enzyme activities of Cu, Zn-superoxide dismutase (Cu,Zn-SOD), Mn-superoxide dismutase (Mn-SOD), catalase, and glutathione peroxidase (GPx) in the skin fibroblasts. The activities of Cu,Zn-SOD, catalase and glutathione peroxidase were found to decrease with age. However, the activity of Mn-SOD was increased with age before 60 years but was decreased thereafter. Moreover, the activity ratios of Mn-SOD/catalase and Mn-SOD/GPx exhibited the same pattern of change with age. This indicates that free radical scavenging enzymes can effectively dispose of ROS and free radicals before 60 years of age. However, elevated oxidative stress caused by an imbalance between the production and removal of ROS and free radicals occurred in skin fibroblasts after 60 years of age. Taken together, we suggest that the functional decline of free radical scavenging enzymes and the elevation of oxidative stress may play an important role in eliciting oxidative damage and mutation of mtDNA during the human aging process.

8-Hydroxy-2'-Deoxyguanosine↗

Potential of denaturing gradient gel electrophoresis for scanning of beta-thalassemia mutations in India.

Over the last few years, substantial progress has been made in developing strategies for the detection and characterization of various mutations causing beta-thalassemia. The Indian population comprises of numerous endogamous caste groups and beta-thalassemia is seen in almost all of them. Knowledge of the spectrum of beta-thalassemia mutations in the population is a prerequisite for successful implementation of a prevention programme. Among the different approaches available today, Denaturing Gradient Gel Electrophoresis (DGGE) offers a valid technical approach which is applicable for screening of known mutants and polymorphisms as well as in locating regions of DNA bearing unknown mutations. We analysed 356 unrelated beta-thalassemia heterozygotes by DGGE and detected 30 anomalous DGGE patterns. Fifteen mutations were characterized after sequencing 25 anomalous patterns. Of these, codon 10(GCC --> GCA) is a recently reported novel beta-thalassemia mutation while -28(A --> G) and codon 121(G --> T) are being reported for the first time in the Indian population. HbS and HbE also showed two anomalous DGGE patterns each. Framework (FW) linkage studies showed that four mutations were associated with different beta-globin gene frameworks. Linkage of IVSI-5(G --> C) and cap site +1(A --> C) to FW2 and 619-bp deletion to FW1 is being observed for the first time. Multiple DGGE patterns corresponding to the same mutation is one of the major drawbacks of this technique. In spite of this, if sufficient preliminary work has been carried out to compile a comprehensive catalogue of DGGE patterns; this is a powerful approach to characterize the mutation or to localize a small region of DNA in the case of rarer mutations.

Base Sequence↗

Syngeneic renal transplantation increases the number of renal dendritic cells in the rat.

Dendritic cells participate in the regulation of CD4 and CD8 T cells during transplant rejection. Understanding what causes increased numbers of dendritic cells to appear in the renal transplant is therefore important. We performed syngeneic renal transplants between rats. We used the monoclonal antibody OX62 to detect dendritic cells, and OX6 to detect major histocompatability complex (MHC) Class II in the renal transplant. One week after transplant, dendritic cells appeared. This indicates that the injury of transplantation itself is sufficient to increase the number of dendritic cells in the kidney in a model where there is no alloreactivity.

Animals↗

Genetic polymorphism of the mannose-binding protein gene in children with sickle cell disease: identification of three new variant alleles and relationship to infections.

Mannose-binding protein (MBP) is a serum lectin that participates in the innate immune response. MBP deficiency may constitute a risk factor in the development of infections. Three MBP structural variants have been identified with a dominant effect on MBP serum concentration. Similarly, polymorphisms in the promoter of the corresponding gene (HSMBP1B) have been related to variations of MBP concentration in serum. Children with sickle cell disease (SCD) have an increased susceptibility to infections with encapsulated organisms resulting in meningitis, septicaemia, and osteomyelitis. We have investigated the HSMBP1B genotype in 242 children with SCD living in Paris. Apart from the known variant alleles, we identified three novel ones and report their distribution in our sample population. In addition, we found rather unexpectedly an increased frequency of the variant alleles in patients who had not suffered severe infections.

Adolescent↗

Hypothesis: is renal allograft rejection initiated by the response to injury sustained during the transplant process?

Allograft rejection can be caused by numerous factors such as damage to the donor kidney during surgical removal or implantation, injury sustained during the transport process between the donor and recipient, and suboptimal allograft perfusion during the intra- and post-operative period. In cadaveric allografts, damage can occur during cold storage, during the transit stage between donor and recipient, and hemodynamic instability due to the initial damage that caused its removal from the donor (such as brain death or trauma). We hypothesize that rejection requires recognition of this injury in addition to recognition of alloantigens. If indeed injury proves to be one factor in acute rejection episodes, then therapeutic efforts can be made to reduce injury during the transplantation process.

Cell Differentiation↗

Transplant surgery injury recruits recipient MHC class II-positive leukocytes into the kidney.

BACKGROUND: CD4 T cells, which are stimulated by the "indirect pathway" of antigen-presentation, participate in rejection. These T cells are sensitized by recipient major histocompatibility complex (MHC) class II-positive leukocytes that migrate into the transplant. Therefore, an important early step in rejection is the immigration of these recipient MHC class II-positive leukocytes into the renal transplant. The regulation of this early step is not understood. We now test the hypothesis that such leukocytes immigrate into the renal transplant in response to ischemic injury occurring during the transplant procedure. METHODS: We transplanted Brown Norway (BN) kidneys into F1 Lewis/Brown Norway (L/BN) recipients. The F1 recipients are tolerant to the parental BN antigens, and any infiltration of recipient MHC class II-positive leukocytes results from injury occurring during transplantation surgery. In addition, ischemia/reperfusion injury was also induced by temporarily occluding the native renal arteries for 30 minutes. Transplanted kidneys and native kidneys, which suffered ischemia/reperfusion injury, were studied by immunohistochemistry on days 3, 7, 14, and 28 after surgery. Staining by the new monoclonal antibody (mAb) OX62 and antibodies to MHC class II identified dendritic cells. In addition, the following monoclonal antibodies identified: gamma/delta T cells, V65; B cells, OX33; cells that may be macrophages, dendritic cells, or dendritic cell precursors, ED1 (+) and OX62 (-); and recipient class II MHC, OX3. RESULTS: After transplantation, the serum creatinine increased to 4 mg/dl and then decreased, which was consistent with reversible injury during transplantation and the absence of rejection. We found that the injury of transplantation itself resulted in the infiltration of recipient MHC class II-positive leukocytes into the transplanted kidney. This infiltrate peaked at days 7 to 14 after surgery. The inflammation was peritubular and patchy and involved cortex and outer medulla. Double staining for OX62 and OX3 identified some of the infiltrating leukocytes as dendritic cells. Other recipient leukocytes were MHC class II positive, ED1 positive, and OX62 negative. We also found that MHC class II leukocytes, including dendritic cells, infiltrated native kidneys injured by ischemia/reperfusion injury. CONCLUSION: To our knowledge, this is the first demonstration that injury to the kidney during transplantation recruits recipient MHC class II-positive leukocytes into the kidney. Some of these leukocytes are dendritic cells.

Animals↗

Endoscopic hydrogen peroxide spray may facilitate localization of the bleeding site in acute upper gastrointestinal bleeding.

BACKGROUND AND STUDY AIMS: A major problem encountered in the emergency endoscopic management of acute upper gastrointestinal (UGI) bleeding is poor localization of the bleeding site, which can be obscured by blood or clots. Traditional attempts to overcome this problem have been by physical methods, which have usually proved unsatisfactory. The aim of this prospective study was to show that hydrogen peroxide can be used as a dissolution agent, resulting in an alteration of the characteristics of blood clots and allowing a clearer visual field. PATIENTS AND METHODS: Twenty patients with acute UGI bleeding (13 male, seven female) were included in the study. The suspected site of bleeding was initially sprayed with 200 ml of saline and then with 25-175 ml of 3 % H2O2. Pictures of the visual field were taken before and after irrigation with both saline and H2O2. These pictures were evaluated by three gastroenterologists and scored using the following visual clearance scoring system: -3, marked worsening of visual field; -2, moderate worsening; -1, slight worsening; 0, no change; +1, slight improvement; +2, moderate improvement; + 3, marked improvement. In cases of active oozing or spurting, after initial hemostasis was achieved the bleeding point was injected with pure ethanol or cauterized with a heater probe. In order to assess the safety of 3 % H2O2 endoscopic biopsies of the antrum and the duodenal bulb were performed before and 30 minutes after its use and examined by a pathologist. RESULTS: There was a significant improvement in the mean visual clearance score after irrigation with H2O2 compared to irrigation with saline alone (2.13 vs. 0.43, P<0.001). During endoscopic examination there were 19 patients with active oozing from the ulcer base covered by an adherent blood clot; 12 of these (63.1%) achieved initial hemostasis after H2O2 spraying. Eleven of 18 (61.1 %) patients complained of a mild epigastric burning sensation during H2O2 irrigation. There was no clinically significant change in the histology of the antrum and the duodenal bulb after H2O2 therapy. CONCLUSIONS: We concluded that H2O2 is a safe and effective way to clear the visual field, facilitating the localization of the bleeding site during emergency endoscopy for acute UGI bleeding, with only mild side effects. In some cases H2O2 therapy can also induce temporary hemostasis. We recommended the use of hydrogen peroxide to improve endoscopic visualization, especially in cases where an adherent blood clot covers the suspected bleeding site.

Adult↗

Interaction of hydroxycinnamic acid derivatives with the Cl3COO radical: a pulse radiolysis study.

The electron transfer reactions between the trichloromethylperoxyl radical (Cl3COO*) and hydroxycinnamic acid derivatives, including chlorogenic acid, sinapic acid, caffeic acid, ferulic acid and 3,4-(methylenedioxy)cinnamic acid, have been studied by pulse radiolysis. The hydroxycinnamic acid derivatives, especially sinapic acid, are identified as good antioxidants for reduction of Cl3COO* via electron transfer reactions. From buildup kinetic analysis of phenoxyl radical, the rate constant for reaction of Cl3COO* with sinapic acid has been determined to be 8.2x10(7) dm3 mol(-1) s(-1), while the rate constants of electron transfer from other hydroxycinnamic acid derivatives to Cl3COO* were obtained to be about 2x10(7) dm3 mol(-1) s(-1). The reaction of 3,4-(methylenedioxy) cinnamic acid with Cl3COO* was investigated as an evidence for the electron transfer mechanism.

Antioxidants↗

Phase separation of rigid-rod suspensions in shear flow.

We analyze the behavior of a suspension of rigid-rod-like particles in shear flow using a modified version of the Doi model, and construct diagrams for phase coexistence under conditions of constant imposed stress and constant imposed strain rate, among paranematic, flow-aligning nematic, and log-rolling nematic states. We calculate the effective constitutive relations that would be measured through the regime of phase separation into shear bands. We calculate phase coexistence by examining the stability of interfacial steady states and find a wide range of possible "phase" behaviors.

Journal Article↗

Factors influencing resistance to reinfection with Plasmodium falciparum.

A treatment-reinfection study design was used to investigate the relationships between host immunologic and/or genetic factors and resistance to reinfection with Plasmodium falciparum. Sixty-one children in Gabon were enrolled in a cross-sectional study to measure the prevalence of each human plasmodial species. All were given amodiaquine for radical cure of parasites, and 40 were subsequently followed-up for 30 weeks. Successive blood smears were examined to measure the delay of reappearance in blood of asexual stages of P. falciparum parasites. Presence of infection during the cross-sectional survey was associated with male sex, non-deficient glucose-6-phosphate dehydrogenase activity, plasma interleukin-10 level, and anti-LSA-Rep antibody concentration. Resistance to reinfection was related to the presence of anti-LSA-J antibodies, and the absence of anti-LSA-Rep antibodies. Moreover, P. malariae-infected subjects were usually co-infected with P. falciparum, and were also more rapidly reinfected with P. falciparum after treatment, compared with those without P. malariae infection.

Adolescent↗

The hemodynamic changes of gastroduodenal regional blood flow after Helicobacter pylori eradication in patients with duodenal ulcer scar.

Duodenal ulcer (DU) is frequently accompanied by Helicobacter pylori (Hp) infection and associated with the imbalance of aggressive factors and defensive factors. To investigate the possible relationship between Hp and regional gastric blood flow, 26 endoscopically proved DU (scar stage) and Hp infection patients were included and received triple therapy (colloid bismuth subcitrate 120 mg qid for 4 weeks, amoxicillin 500 mg qid for 2 weeks and metronidazole 250 mg tid for 2 weeks). Regional gastroduodenal blood flow (RGDF) was measured at DU scar area and antrum lesser curvature site by laser Doppler flowmetry during endoscopic examination, before and one month after triple therapy. In 22 patients with Hp eradication the RGDF was significantly elevated at antrum lesser site after triple therapy (p < 0.05) but there was no difference at DU scar area. However, in 4 patients without Hp eradication no difference of RGDF in these two points was found. Therefore, Hp appears to have direct effects on gastric microcirculation.

Adult↗

Unexpected transurethral resection of prostate syndrome complicated with acute myocardial infarction during transurethral incision procedure--a case report.

Transurethral incision (TUI) is a simple and safe procedure. We, herein, present a case undergoing transurethral incision procedure during which he developed transurethral resection of prostate syndrome (TURP syndrome) and hypothermia precipitating an acute perioperative myocardial infarction attack. The potential risk of development of TURP syndrome in settings other than TURP surgery as well as its prevention are reviewed and discussed.

Aged↗

Immunogenicity of oral poliovirus vaccine in Taiwan.

Previous studies have shown that the immune response to trivalent oral poliovirus vaccine (OPV) varies widely from country to country. However, there has been no report on the immunogenicity of this vaccine in Taiwanese children. In this study, 98 children were followed up for 17 months to study the antibody responses following four doses of trivalent OPV. The results showed that, after two doses of vaccine, all children were protected against poliovirus type 1 and 2. All except two children also developed protective antibodies against poliovirus type 3. After three doses, the antibody levels in all subjects were above protective concentrations. The fourth dose, given at 18 months of age, further boosted the antibody titers. These findings show that the OPV currently used in Taiwan is highly immunogenic in Taiwanese children.

Antibodies, Viral↗

Penicillin-nonsusceptible Streptococcus pneumoniae infections in children.

The emergence of penicillin-nonsusceptible Streptococcus pneumoniae (PNSSP) has brought a new clinical challenge. In Taiwan, reports of the prevalence and clinical features of PNSSP infections in children are limited. This study reviewed the resistance patterns of all clinical isolates of S. pneumoniae obtained from patients under 17 years of age from January 1993 through July 1998 in a medical center. Their clinical features and treatment responses were analyzed, with special attention paid to those patients with invasive PNSSP infections. Totally, 170 clinical isolates of S. pneumoniae were obtained from 168 patients aged under 17 years. Among those infections, there were 56 sinusitis (including 4 sinusitis with bacteremia), 44 pneumonia (including 23 pneumonia with bacteremia or empyema), 23 otitis media (including 5 otitis media with bacteremia), 9 simple bacteremia, 9 conjunctivitis, 8 meningitis, 4 peritonitis, 3 skin infections and the other 14 isolates were colonization. One hundred eleven isolates (65.3%) showed reduced penicillin susceptibility by the disk diffusion method. A trend of increasing percentiles of PRSP was noted: 27.3% (3/11) in 1993, 37.5% (9/24) in 1994, 55.5% (10/18) in 1995, 77.5% (31/40) in 1996, 66.0% (31/47) in 1997, and 87.1% (27/31) in 1998. Minimum inhibitory concentration (MIC) determinations by the E-test showed some of the isolates were intermediately resistant. Prior antibiotic usage was associated with a higher incidence of PNSSP infections. However, most children responded well to antimicrobial treatment.

Adolescent↗

Aging- and smoking-associated alteration in the relative content of mitochondrial DNA in human lung.

mtDNA mutations and oxidative DNA damage has been observed to accumulate in the lung and other tissues in human aging. Thus, it is of interest to know whether the content of mtDNA is changed in aging tissues of the human. Using a competitive PCR method, we determined the relative content of mtDNA in the lung tissues of 49 subjects aged 16-85 years. The results showed that the relative content of mtDNA (with respect to the beta-actin gene) in the lung tissues was significantly increased with age (P < 0.005). The average mtDNA content in the lung tissues of the subjects over 80 years of age was found to be about 2.6-fold higher than that of the subjects below age 20. However, the relative content of mtDNA was slightly increased in the lung tissues of light smokers but significantly decreased in heavy smokers. Moreover, we found a significant increase with age in the level of oxidative damage to DNA as indicated by the ratio of 8-OH-dG/dG in total DNA (P < 0.0005). These results together with our previous findings suggest that the increase in mtDNA content of aging tissues may be effected through a feedback mechanism to compensate for the functional decline of mitochondria in human aging and that smoking may modulate the mechanism.

8-Hydroxy-2'-Deoxyguanosine↗

Natural infection of a homozygous delta24 CCR5 red-capped mangabey with an R2b-tropic simian immunodeficiency virus.

A homozygous 24-bp deletion (Delta24) was found in the CC chemokine receptor 5 (CCR5) of 11 out of 15 red-capped mangabeys (RCMs), Cercocebus torquatus torquatus, both in Africa and in an American zoo. The CCR5 Delta24 defect encompassed eight amino acids in frame in the fourth transmembrane region. Unexpectedly, RCM-009, one of 11 homozygotes (Delta24CCR5/ Delta24CCR5), was found to be naturally infected with a divergent simian immunodeficiency virus (SIV) strain, which was not R5-tropic, but used CCR2b (R2b) as its major coreceptor. SIVrcmGab1 was the only R2b-tropic SIV among other divergent SIVs tested. Cells transfected with the Delta24 CCR5 did not support entry of R5-tropic SIVmac, SIVcpz, SIVmne, HIV-2, or HIV-1, and were also inactive in signal transduction mediated by beta-chemokines. At 86.6%, the Delta24 allelic frequency was significantly higher than that of the 32-bp deletion found in humans. The Delta24 frequency was 4.1% in 34 sooty mangabeys (SMs), a geographically isolated subspecies that was naturally infected with R5-tropic SIV. Finding identical deletions in two mangabey subspecies separated for 10,000 years or more dates the Delta24 CCR5 deletion as ancient. However, the source of the selective pressure for the high rate of CCR5 deletion in RCMs remains to be determined. The high allelic frequency of the Delta24 CCR5 in RCMs, in comparison to that of SMs, suggests that R2b-tropism may have been acquired by SIVrcm, as an adaptation to CCR5 genetic defects appeared in its host.

Amino Acid Sequence↗