PubMed HealthSearch

Biomedical subjects

Y Mao

Publications and source records attributed to Y Mao.

At least 19 recordsLinked to original sources

Two-stage sampling for etiologic studies. Sample size and power.

Preexisting computerized databases are potentially valuable sources of epidemiologic data. Since such databases are infrequently created specifically for etiologic research, data may be available for the exposure of interest and, through record linkage, for the endpoint of interest, but lacking for potential confounders. Because of the size of these databases, two-stage sampling is an efficient alternative to surveying the entire study population for confounder data. At stage 1, information on exposure and disease status is obtained for the entire study population. Confounder data are collected for probability-selected subsamples at stage 2. Logistic regression is performed on the stage 2 samples, with the parameter estimates and variances appropriately corrected to account for the stage 1 data. In this paper, the authors present methods for determining the required stage 2 sample size in the case of categorical exposure and confounding variables. Sample size tables, power curves, and a computer program have been produced to accommodate a binary exposure and a single binary confounder. With the increasing availability of preexisting yet incomplete databases, the potential for use of two-stage sampling will greatly increase in the future. This investigation provides a basis for estimating the number of participants to sample for the collection of confounder data at the second stage.

Case-Control Studies

A Study of the Adsorption of Acrylic Acid and Maleic Acid from Aqueous Solutions onto Alumina

The adsorption of acrylic acid and maleic acid on alumina was studied, and it has been found that the adsorption obeys the Langmuir isotherm. The adsorption of the acids is dependent on the pH of the solutions. For acrylic acid, the optimal pH is 4.5; for maleic acid, the optimal pH is 1.1-1.6. These pH values are close to the pKa for acrylic acid and pKa 1 for maleic acid, respectively. The maximum amount of each acid adsorbed at its optimal pH was obtained by fitting the adsorption data to the Langmuir isotherm, and the values are 727 &mgr;mol/g for acrylic acid and 525 &mgr;mol/g for maleic acid. These values are consistent with monolayer adsorption. Solid state 13 C NMR was used to investigate the nature of the adsorption. It is suggested that the adsorbed carboxylic acids are present in the undissociated form.

Journal Article

A case-control study of diet and lung cancer in northeast China.

A case-control study involving interviews with 227 lung-cancer cases and 227 matched hospital controls was conducted in Heilongjiang Province in northeast China to examine the influence of dietary factors on the risk of developing lung cancer. Lung-cancer cases were all incident cases judged to be suitable candidates for tumor removal by surgery. Controls were selected among hospitalized patients with non-neoplastic and non-lung disease. The overall male lung-cancer risks associated with cigarette smoking were similar to those reported in other Chinese studies but quite low compared to risks in Western countries. However, the subjects in this study were relatively young (average age 53.2), had started to smoke on average at a relatively old age (21.3 years), and only smoked an average of 18.7 cigarettes per day. Lung-cancer risk was not strongly associated with any of the nutrients examined, when all cases were compared to all controls. However, the data were suggestive of differences in the relationship of diet to risk among smokers and non-smokers. Cautious interpretation is required because of the wide confidence intervals due to limited sample size. Among the smokers, only higher beta-carotene was associated with estimates suggesting a lowered risk. Among non-smokers, the evidence suggested that increased vegetable consumption might reduce risk, consumption of any fruit might reduce risk but beta-carotene was unrelated to risk. The differences observed in the relationship of diet to lung-cancer risk between Chinese smokers and non-smokers warrant further study.

Case-Control Studies

Induction of DNA topoisomerase II-mediated DNA cleavage by beta-lapachone and related naphthoquinones.

Recent studies have suggested that 3,4-dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5,6-dione (beta-lapachone) inhibits DNA topoisomerase I by a mechanism distinct from that of camptothecin. To study the mechanism of action of beta-lapachone, a series of beta-lapachone and related naphthoquinones were synthesized, and their activity against drug-sensitive and -resistant cell lines and purified human DNA topoisomerases as evaluated. Consistent with the previous report, beta-lapachone does not induce topoisomerase I-mediated DNA breaks. However, beta-lapachone and related naphthoquinones, like menadione, induce protein-linked DNA breaks in the presence of purified human DNA topoisomerase IIalpha. Poisoning of topoisomerase IIalpha by beta-lapachone and related naphthoquinones is independent of ATP and involves the formation of reversible cleavable complexes. The structural similarity between menadione, a para-quinone, and beta-lapachone, an ortho-quinone, together with their similar activity in poisoning topoisomerase IIalpha, suggests a common mechanism of action involving chemical reactivity of these quinones. Indeed, both quinones form adducts with mercaptoethanol, and beta-lapachone is 10-fold more reactive. There is an apparent correlation between the rates of the adduct formation with thiols and of the topoisomerase II-poisoning activity of the aforementioned quinones. In preliminary studies, beta-lapachone and related naphthoquinones are found to be cytotoxic against a panel of drug-sensitive and drug-resistant tumor cell lines, including MDR1-overexpressing cell lines, camptothecin-resistant cell lines, and the atypical multidrug-resistant CEM/V-1 cell line.

Antineoplastic Agents, Alkylating

Structural interactions of the oligomycin sensitivity-conferring protein in the yeast ATP synthase.

The structure/function relationship of oligomycin sensitivity-conferring protein (OSCP), subunit 5 of the mitochondrial ATP synthase, from yeast Saccharomyces cerevisiae has been studied by a combination of genetic and biochemical methods. OSCP was studied by deletion mutagenesis of the N- and C-terminal regions by modifying the gene coding for OSCP. Two deletion mutations were made immediately downstream of the leader peptide of OSCP and five were made at the C-terminus. OSCP was functional with deletions of amino acids 3 to 17 (ND15) and of the last 8 amino acids (CD8), while deletion of amino acids 3 to 31 (ND29) and the last 9 amino acids (CD9) inactivated the ATP synthase, as determined by in vivo analysis. The deletion mutants were expressed in Escherichia coli, purified, and studied by in vitro reconstitution studies. Circular dichroism studies suggested that the mutant proteins, with the possible exception of ND29, were folded in a similar fashion as wild-type OSCP. Mutants ND15 and CD8 were able to reconstitute an oligomycin-sensitive ATPase complex, although not as well as wild-type OSCP, while ND29 and CD9 were completely ineffective. Binding studies of ND29 and CD9 indicate that these mutants in OSCP were unable to bind to the membrane portion of the ATP synthase, F0, and these results were supported by competition binding studies. These results support the hypothesis that the N- and C-terminal regions of subunit 5 interact with F0 and suggest that the central region interacts with F1.

Adenosine Triphosphatases

The monosodium glutamate symptom complex: assessment in a double-blind, placebo-controlled, randomized study.

BACKGROUND: Considerable debate swirls about the validity of symptoms described by many people after ingestion of monosodium glutamate (MSG), and the question has remained unresolved largely because of a paucity of well-designed challenge studies. METHODS: We conducted oral challenge studies in self-identified MSG-sensitive subjects to determine whether they had a statistically significant difference in the incidence of their specific symptoms after ingestion of MSG compared with placebo. First, 5 gm MSG or placebo was administered in random sequence in a double-blind fashion. Subjects who reacted only to a single test agent then underwent rechallenge in random sequence in a double-blind fashion with placebo and 1.25, 2.5, and 5 gm MSG. A positive response to challenge was defined as the reproduction of > of 2 of the specific symptoms in a subject ascertained on prechallenge interview. RESULTS: Sixty-one subjects entered the study. On initial challenge, 18 (29.5%) responded to neither MSG nor placebo, 6 (9.8%) to both, 15 (24.6%) to placebo, and 22 (36.1%) to MSG (p = 0.324). Total and average severity of symptoms after ingestion of MSG (374 and 80) were greater than respective values after placebo ingestion (232 and 56; p = 0.026 and 0.018, respectively). Rechallenge revealed an apparent threshold dose for reactivity of 2.5 gm MSG. Headache (p < 0.023), muscle tightness (p < 0.004), numbness/tingling (p < 0.007), general weakness (p < 0.040), and flushing (p < 0.016) occurred more frequently after MSG than placebo ingestion. CONCLUSIONS: Oral challenge with MSG reproduced symptoms in alleged sensitive persons. The mechanism of the reaction remains unknown, but symptom characteristics do not support an IgE-mediated mechanism. According to Food and Drug Administration recommendations, the symptoms, originally called the Chinese restaurant syndrome, are better referred to as the MSG symptom complex.

Administration, Oral

Hemodialysis versus peritoneal dialysis: a comparison of adjusted mortality rates.

Although kidney transplantation is the preferred treatment method for patients with ESRD, most patients are placed on dialysis either while awaiting transplantation or as their only therapy. The question of which dialytic method provides the best patient survival remains unresolved. Survival analyses comparing hemodialysis and continuous ambulatory peritoneal dialysis/continuous cyclic peritoneal dialysis (CAPD/CCPD), a newer and less costly dialytic modality, have yielded conflicting results. Using data obtained from the Canadian Organ Replacement Register, we compared mortality rates between hemodialysis and CAPD/CCPD among 11,970 ESRD patients who initiated treatment between 1990 and 1994 and were followed-up for a maximum of 5 years. Factors controlled for include age, primary renal diagnosis, center size, and predialysis comorbid conditions. The mortality rate ratio (RR) for CAPD/CCPD relative to hemodialysis, as estimated by Poisson regression, was 0.73 (95% confidence interval: 0.68 to 0.78). No such relationship was found when an intent-to-treat Cox regression model was fit. Decreased covariable-adjusted mortality for CAPD/CCPD held within all subgroups defined by age and diabetes status, although the RRs increased with age and diabetes prevalence. The increased mortality on hemodialysis compared with CAPD/CCPD was concentrated in the first 2 years of follow-up. Although continuous peritoneal dialysis was associated with significantly lower mortality rates relative to hemodialysis after adjusting for known prognostic factors, the potential impact of unmeasured patient characteristics must be considered. Notwithstanding, we present evidence that CAPD/CCPD, a newer and less costly method of renal replacement therapy, is not associated with increased mortality rates relative to hemodialysis.

Adolescent

Bet1p activates the v-SNARE Bos1p.

Bet1p is a type II membrane protein that is required for vesicular transport between the endoplasmic reticulum and Golgi complex in the yeast Saccharomyces cerevisiae. A domain of Bet1p, that shows potential to be involved in a coiled-coil interaction, is homologous to a region of the neuronal protein SNAP-25. Here, we used in vitro binding studies to demonstrate that Bet1p plays a role in potentiating soluble NSF attachment protein receptor (SNARE) interactions. Mutational analysis points to the coiled-coil region as necessary for Bet1p function, and circular dichroism experiments support this theory. In vitro binding studies were also used to demonstrate that a direct interaction between Bet1p and Bos1p is required for the efficient interaction of the vesicle SNARE with its SNARE target. Genetic studies suggest that the interactions of Bet1p with Bos1p are regulated by the small GTP-binding protein Ypt1p.

Amino Acid Sequence

Factors affecting the severity of motor vehicle traffic crashes involving young drivers in Ontario.

OBJECTIVES: To assess the factors affecting the severity of motor vehicles traffic crashes involving young drivers in Ontario. POPULATION: Ontario young drivers, aged 16 to 20, involved in traffic crashes resulting in injury, between 1 January 1988 and 31 December 1993, on public roads in Ontario. METHODS: Population based case-control study. Cases were fatal injury, major injury, and minor injury crashes involving young drivers. Controls were minimal injury crashes involving young drivers. Cases and controls were obtained retrospectively from the Canadian Traffic Accident Information Databank. Unconditional logistic regression was used for data analysis. RESULTS: Factors significantly increasing the risk of fatal injury crashes include: drinking and driving (odds ratio (OR) 2.3), impairment by alcohol (OR 4.8), exceeding speed limits (OR 2.8), not using seat belts (OR 4.7), full ejection from vehicle (OR 21.3), intersection without traffic control (OR 2.2), bridge or tunnel (OR 4.1), road with speed limit 70-90 km/hour (OR 5.6) or 100 km/hour (OR 5.4), bad weather (OR 1.6), head-on collision (OR 80.0), and overtaking (OR 1.9). Results of the same model applied to major and minor injury crashes demonstrated consistent but weaker associations with decreasing levels of crash severity. CONCLUSIONS: A casual relationship between crash severity and the risk factors listed above was proposed. Risk factors recommended for preventive intervention include: alcohol consumption, speeding, and use of seat belts. Head-on collisions are of primary concern.

Accidents, Traffic

Elastase contributes to antigen-induced mucociliary dysfunction in ovine airways.

Antigen-induced bronchoconstriction is associated with impairment of mucociliary clearance with a time course that is consistent with the initial influx of neutrophils into the airway. In this study we tested the hypothesis that elastase released from activated neutrophils contributes to the acute (0 to 6-hr) antigen-induced mucociliary dysfunction. Tracheal mucous velocity CTMV), an index of mucociliary function, was measured with a roentgenographic technique before and serially after airway challenge with Ascaris suum antigen alone, or after pretreatment with aerosolized alpha1-protease inhibitor (alpha1-PI, 10 mg) or the specific neutrophil elastase inhibitor ICI 200,355 (10 mg). Antigen alone significantly decreased TMV. Treatment with either alpha1-PI or ICI 200,355, given either at 30 min before antigen challenge or 1 h after challenge, significantly attenuated the antigen-induced reduction in TMV at 6 h after challenge, whereas sheep treated with inactivated alpha1-PI were not protected from this antigen-induced event. Inhalation of ovine elastase (obtained from stimulated neutrophils) significantly decreased TMV, and this effect was also blocked by pretreatment with alpha1-PI. Both alpha1-PI and ICI 200,355 inhibited the activity of elastase obtained from stimulated ovine neutrophils. To verify that the neutrophil numbers and elastase activity increased in sheep airways after antigen challenge, nine animals underwent bronchoalveolar lavage (BAL) at 2 h and 4 h after instillation of A. summ antigen. Four hours after challenge, the number of neutrophils had increased by 50-fold, and free elastase activity in lavage fluid had increased. These data indicate that the antigen-induced impairment of mucociliary clearance is partly dependent on increased elastase activity, and that elastase inhibitors may be useful in protecting against mucociliary dysfunction.

Allergens

Changes in the permselectivity of human teeth during caries attack.

Previous studies have shown that enamel permselectivity can influence fluid composition within caries lesions during de- and remineralization. The permselectivity of human enamel, cementum, and dentin sections was examined, in a microwell model, by measurement of the membrane potential developed by KCl diffusion while the sections were immersed in solutions simulating resting (pH = 5.6) and cariogenic plaque fluid (pH = 4.8). In a second experiment, the effects of charged compounds (phytate and Zonyl-FSC) on the tooth permselectivity were examined. The average membrane potentials (+/- SD) in "resting plaque" solution were: sound enamel, 18.9 +/- 3.2 mV, n = 66; dentin, 0.9 +/- 9.2 mV, n = 59; and cementum, -0.8 +/- 8.2 mV, n = 42, with a positive sing indicating cation selectivity. The average membrane potentials became more negative in "cariogenic plaque" solution for all types of sections: sound enamel, 5.2 +/- 2.1 mV, n = 46; dentin, -8.1 +/- 7.4 mV, n = 45; and cementum, -14.3 +/- 8.0 mV, n = 34. In lesion enamel sections, the membrane potential was reduced from the non-lesion wells in both types of test solutions, while phytate treatment caused an increase of approximately 10 mV in potential (increased cation selectivity) in every enamel well in either "resting" or "cariogenic" solution. Treatment of enamel sections with Zonyl-FSC caused the membrane potential to become more negative in both test solutions, with many of the wells showing anion selectivity in the cariogenic "plaque-like" solution. However, the changes in enamel membrane potentials induced by Zonyl-FSC slowly increased toward the initial values after treatment, while the effects of the phytate pre-treatment persisted. Most dentin sections treated with phytate also showed an increase in potential after phytate treatment; however, Zonyl-FSC seemed to have little effect on the membrane potential of dentin. The results of this study suggest that modification of tooth permselectivity by surface-active agents may be a viable method of decreasing the rate of caries progression.

Dental Caries

Increased overnight fluoride concentrations in saliva, plaque, and plaque fluid after a novel two-solution rinse.

Recent studies showed that salivary, plaque-fluid, and whole-plaque fluoride were significantly higher 120 min after subjects rinsed with a novel two-solution rinse than after they rinsed with a NaF rinse of the same fluoride concentration. In this study, the persistence of these increases was investigated overnight, a period of time that is more clinically relevant. Improved analytical techniques for the ultramicro determination of whole-plaque and plaque-fluid fluoride from the same sample are also described. Thirteen subjects abstained from toothbrushing for 48 hrs and rinsed for 1 min with a 12 mmol/L (228 ppm) NaF or the two-solution rinse before bedtime. Samples were then collected the following morning before breakfast: (1) Saliva samples were either clarified by centrifugation or acid-extracted with 1 mol/L HClO4; and (2) single-site molar plaque samples were centrifuged to obtain plaque fluid and/or extracted with 1 mol/L HClO4. Results showed that, compared with NaF, the two-solution rinse produced significantly higher fluoride concentrations in all samples: The concentration of fluoride in whole plaque and whole saliva following the new rinse exceeded concentrations found after the NaF rinse by factors of three and four, respectively, while in plaque fluid, the two-solution rinse produced about a two-fold increase over NaF values, which were near baseline levels. This increase, however, was only about 20% in centrifuged saliva. The increases in saliva and especially in plaque-fluid fluoride after the two-solution rinse indicate a greater remineralization potential, while the enhanced fluoride reservoirs found in plaque overnight after this rinse constitute a reserve that may release fluoride into the plaque fluid over an extended period of time.

Adult

[Study on transposition behavior of IS5376 in Bacillus stearothermophilus].

IS5376 and IS5377 are two transposable elements discovered in Bacillus stearothermophilus. Analysis of random samples revealed that the frequency of transposition of IS5376 from CU21 chromosome to plasmids pFDC5 and pFDC12 was much higher at 65 degrees C than that at 48 degrees C while that of IS5377 was very low at both 48 degrees C and 65 degrees C. The exact nature of the temperature effect is obscure at present from evidences obtained so far it is concluded that this is a consequence of the innate property of IS5376. Furthermore, it was found that a certain degree of site specificity in transposition was evident and that a direct repeat of 4 or 5 bp of the target DNA appeared at the site of transposition.

Base Sequence

[Constuction of an improved system for the determination of fidelity of polymerase in PCR].

A system used for the determination of fidelity of DNA polymerase in PCR was developed in E.coli and was used to determine the fidelity of FD DNA polymerase in PCR amplication. Frame shift and base substitution mutations were created in vitro in the lacZ gene in pUC118 and pUC119. As a result, a set of six derived plasmids namely pFDFM118 and pFDFM119 (-1 frame shift), pFDFP118 and pFDFP119 (+1 frame shift), pFDFU118 and pFDFU119 (base substitution) were obtained. All of them failed to carry out lacZ alpha-complementation in E.coli MV1184 and the colonies appeared white on medium with X-Gal and IPTG consequently. PCR reaction was carried out using these derived plasmids as templates and the PCR products were ligated to specially constructed cloning vectors pFDFL118 or pFDFL119, and the ligated products were used to transform MV1184. If any back mutation happens to occur during PCR, the transformants would appear blue on medium with X-Gal and IPTG. By scoring the number of blue and white colonies, the fidelity of DNA polymerase can be calculated. With this system the error of replication of the FD DNA polymerase was found to be 10(-5)-10(-6).

Base Sequence

Cervical cancer screening: are the 1989 recommendations still valid? National Workshop on Screening for Cancer of the Cervix.

Although screening for cervical cancer has been shown to be effective in reducing the morbidity and mortality associated with this disease, and despite many attempts to encourage the development of provincial programs, as of 1995 no province had a comprehensive screening program for cervical cancer. Participants at the Interchange '95 workshop, held in Ottawa in November 1995, reviewed the recommendations of the 1989 National Workshop on Screening for Cancer of the Cervix and identified factors that have impeded their implementation. Participants discussed the need for comprehensive information systems, quality control and strategies to increase recruitment of unscreened and underscreened women. They concluded that the formation of a Cervical Cancer Prevention Network involving key stakeholders will facilitate the development and implementation of provincial programs to ensure optimal screening. They agreed that, in the interim, recommendations for practising physicians should remain as they were following the 1989 workshop.

Canada

Vanadium(IV)-mediated free radical generation and related 2'-deoxyguanosine hydroxylation and DNA damage.

Free radical generation, 2'-deoxyguanosine (dG) hydroxylation and DNA damage by vanadium(IV) reactions were investigated. Vanadium(IV) caused molecular oxygen dependent dG hydroxylation to form 8-hydroxyl-2'-deoxyguanosine (8-OHdG). During a 15 min incubation of 1.0 mM dG and 1.0 mM VOSO4 in phosphate buffer solution (pH 7.4) at room temperature under ambient air, dG was converted to 8-OHdG with a yield of about 0.31%. Catalase and formate inhibited the 8-OHdG formation while superoxide dismutase enhanced it. Metal ion chelators, DTPA and deferoxamine, blocked the 8-OHdG formation. Incubation of vanadium(IV) with dG in argon did not generate any significant amount of 8-OHdG, indicating the role of molecular oxygen in the mechanism of vanadium(IV)-induced dG hydroxylation. Vanadium(IV) also caused molecular oxygen-dependent DNA strand breaks in a pattern similar to that observed for dG hydroxylation. ESR spin trapping measurements demonstrated that the reaction of vanadium(IV) with H2O2 generated OH radicals, which were inhibited by DTPA and deferoxamine. Incubation of vanadium(IV) with dG or with DNA in the presence of H2O2 resulted in an enhanced 8-OHdG formation and substantial DNA double strand breaks. Sodium formate inhibited 8-OHdG formation while DTPA had no significant effect. Deferoxamine enhanced the 8-OHdG generation by 2.5-fold. ESR and UV measurements provided evidence for the complex formation between vanadium(IV) and deferoxamine. UV-visible measurements indicate that dG, vanadium(IV) and deferoxamine are able to form a complex, thereby, facilitating site-specific 8-OHdG formation. Reaction of vanadium(IV) with t-butyl hydroperoxide generated hydroperoxide-derived free radicals, which caused 8-OHdG formation from dG and DNA strand breaks. DTPA and deferoxamine attenuated vanadium(IV)/t-butyl-OOH-induced DNA strand breaks.

8-Hydroxy-2'-Deoxyguanosine