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Dominic C Chow

Publications and source records attributed to Dominic C Chow.

9 recordsLinked to original sources

Association between angiotensin-converting enzyme gene polymorphisms and QT duration in a multiethnic population in Hawaii.

OBJECTIVES: Recent studies have suggested that heart-rate corrected QT interval (QTc) in normal populations may be influenced by genetic factors. We report findings of a study of the relationship between QTc, increased QTc (> 440 ms) and angiotensin-converting enzyme (ACE) genotype in a multiethnic, population-based study completed in rural Hawaii. METHODS: Blood samples were obtained while fasting and after an oral glucose challenge from 1452 individuals between 1997 and 2000. The clinical examination included an electrocardiogram. Medical histories, behavioral and socio-demographic information were obtained during the interview. Ethnicity was estimated by self-report. The insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene was determined by polymerase chain reaction (PCR) from a random sample of 588 participants. Multiple linear and logistic regression was used to test for associations between QTc and ACE gene polymorphisms. RESULTS: The overall crude prevalence of increased QTc was 21.2%. The prevalence of increased QTc was lowest among those with ACE DD genotype, and highest among those with ACE insertion/insertion (II) genotype. The adjusted odds ratio for increased QTc was 2.29 (95% CI 1.02-5.12) and 3.61 (95% CI 1.60-8.13) for ID and II genotypes, respectively, compared to the DD genotype. The test for trend was highly significant (p < 0.001). CONCLUSIONS: The ACE insertion allele was associated with increased prevalence of prolonged QTc independent of ethnicity, age, gender, and BMI. These findings may implicate the ACE gene as an important genetic risk factor for cardiovascular disease morbidity and mortality.

Adult↗

Tracking the in vivo fate of recombinant polypeptides by isotopic labeling.

We report a method to incorporate a stable isotope (13C) and a radioactive isotope (14C) into a recombinant polypeptide during Escherichia coli culture in M9 minimal medium supplemented with universally labeled 13C- or 14C-labeled glucose. We chose a thermally responsive elastin-like polypeptide (ELP) as a model polypeptide for this study because of its utility in various biotechnology applications such as drug delivery and tissue engineering. High cell densities were obtained by step-wise adaptation of E. coli to M9 medium in addition to supplementing the medium with trace elements that facilitated growth of E. coli. Furthermore, an optimal concentration of isopropyl-beta-d-thiogalactopyranoside was determined for induction of ELP expression to achieve high yield (mg/L culture) of the ELP. The incorporation of carbon isotopes was stoichiometrically related to the ratio of labeled glucose to unlabeled glucose in the culture medium. The isotope-labeled variants retained the physicochemical properties of the unlabeled ELP, specifically its temperature dependent aggregation behavior. As an example of the utility of this method, the in vitro stability of 14C-labeled ELP in PBS and mouse serum was conveniently quantified by SDS-PAGE and autoradiography. In addition, the in vivo stability of the 14C-labeled ELP in plasma was determined along with its plasma pharmacokinetics.

Autoradiography↗

Ethnic differences in hiv disease progression: a comparison of Asian/Pacific Islanders and Whites living in Hawaii.

OBJECTIVE: To characterize the association of demographic factors with the relative hazards (RH) of developing AIDS or death among HIV-infected individuals of Asian/Pacific Islander (API) ethnicity and Whites. DESIGN: Cohort study SETTING: Hawaii State Health Department database of HIV-infected individuals PATIENTS OR PARTICIPANTS: Hawaii Sero-Positivity and Medical Management (HSPAMM) program participants from January 1989 to November 2002 INTERVENTIONS: None MAIN OUTCOME MEASURES: Differences in the time to develop AIDS or death among HIV-infected individuals who reported being on highly active antiretroviral treatment (HAART) were examined by ethnicity, income, and CD4+ cell counts at HAART initiation by using Kaplan-Meier survival analysis and Cox proportional hazard analyses. RESULTS: The study was based on 516 HIV-infected individuals, who were primarily White (61.0%) and API (21.7%). Whites had a significantly higher CD4+ cell count (P<.01) and income (P<.01) than APIs at enrollment into HSPAMM. Lower income levels and CD4+ cell counts at HAART initiation were strongly associated with an increased RH of developing AIDS or dying. Despite having significantly lower incomes and CD4+ cell counts at enrollment, individuals of API ethnicity do not have an increased RH of developing the outcomes compared to Whites. CONCLUSION: Lower income and CD4+ cell counts at HAART initiation significantly increased the RH of developing AIDS or dying among HIV-infected individuals. Asian/Pacific Islander (API) ethnicity was not a predictor of developing AIDS or dying.

Adult↗

Enzymatic fabrication of DNA nanostructures: extension of a self-assembled oligonucleotide monolayer on gold arrays.

Nucleic acid nanostructures are useful as templates for bionanofabrication of composite molecular nanostructures in materials science, molecular electronics, and biosensing. Here, we demonstrate that terminal deoxynucleotidyl transferase, which repetitively adds mononucleotides to the 3' end of a short DNA initiator, can be used to rapidly fabricate DNA nanostructures up to 121 nm high with lateral dimensions from 0.1 to 4 mum in 2 h. These programmable scaffolds can potentially be employed to build more complex nanostructures consisting of natural or unnatural nucleotides with selective docking sites along the single-stranded DNA.

DNA↗

A descriptive epidemiologic study of HIV-infected individuals in Hawaii: report of the Hawaii Sero-Positivity and Medical Management database (HSPAMM).

This is a retrospective study of the HSPAMM database evaluating differences in clinical, laboratory, HIV-risk factors and demographic characteristics with respect to gender and ethnicity. There were no significant differences comparing gender, and Hawaiians and non-Hawaiians with respect to developing a CD4 count < 200 cells/mm3. HSPAMM contains information on a large number of HIV-infected Asians/Pacific Islanders.

Adolescent↗

Ultra-high expression of a thermally responsive recombinant fusion protein in E. coli.

Elastin-like polypeptides (ELPs) are recombinant peptide-based biopolymers that contain repetitive sequences enriched in glycine, valine, proline, and alanine. Because of the unusually large fraction of these amino acids in ELPs as compared to other cellular proteins, we hypothesized that intracellular pools of these amino acids can be selectively depleted and limit protein yields during expression. In this study, we examined how culture conditions and individual medium components affect protein yields by monitoring cell growth and protein expression kinetics of E. coli expressing an ELP tagged with a green fluorescent protein (GFP). By determining the underlying principles of superior fusion protein yields generated by the hyperexpression protocol, we further improved protein yields through the addition of glycerol and certain amino acids such as proline and alanine and found that amino acid concentrations and the type of basal medium used strongly influenced this beneficial effect. Surprisingly, amino acids other than those that are abundant in ELPs, for example, asparagine, aspartic acid, glutamine, and glutamic acid, also enhanced protein yields even in a nutrient-rich medium. Compared to commonly used Luria-Bertani medium, the protein yield was improved by 36-fold to the remarkable level of 1.6 g/L in shaker flask cultures with a modified medium and optimized culture conditions, which also led to a 8-fold reduction in the cost of the fusion protein. To our knowledge, this is the highest yield of an ELP-fusion protein purified from E. coli cultured in shaker flasks. This study also suggests a useful strategy to improve the yields of other ELP fusion proteins and repetitive polypeptides.

Amino Acids↗

Elevated blood pressure in HIV-infected individuals receiving highly active antiretroviral therapy.

OBJECTIVE: We examined the effects of antiretroviral regimens on blood pressure (BP). METHOD: This retrospective study examined systolic and diastolic BP (SBP and DBP) measurements among participants of a State of Hawaii Department of Health program from January 1995 to July 2001. The change in BP during four consecutive 6-month visits was estimated using linear regression and was interpreted as the change in BP per year. BP changes among the antiretroviral treatment groups were compared to untreated controls. RESULTS: Of 1,601 patients identified, 286 met the criteria for inclusion. After adjustment for baseline age, BP, and CD4+ count, there was an increase in SBP by 4.71 mmHg/year (p =.005) and DBP by 2.26 mmHg/year (p =.076) among patients initiating HAART. Among these patients, an increase of 4.75 mmHg/year in SBP (p =.002) and 1.96 mmHg/year in DBP (p =.042) was seen with HAART regimens containing a protease inhibitor (PI) but no nonnucleoside reverse transcriptase inhibitor (NNRTI). In NNRTI-containing HAART regimens without PIs, an increase of 3.21 mmHg/year in SBP (p =.011) and 2.62 mmHg/year in DBP (p =.050) was observed. No significant BP changes were noted with patients on regimens containing only nucleoside reverse transcriptase inhibitors (NRTIs). CONCLUSION: The use of NNRTI- or PI-containing HAART is associated with elevation of both SBP and DBP in HIV-infected individuals.

Adult↗

Cardiovagal autonomic dysfunction in relation to HIV-associated lipodystrophy.

PURPOSE: Human immunodeficiency virus (HIV)-associated lipodystrophy (LD) may be mediated by changes in the autonomic nervous system. We examined the autonomic function among HIV-infected patients with LD compared to HIV-infected patients without LD (non-LD) and HIV-negative controls (controls). METHOD: This cross-sectional study examined cardiovagal autonomic function among the three groups. LD was defined in HIV-infected patients as increased visceral adipose accumulation and peripheral lipoatrophy. Cardiovagal autonomic testing was assessed by measuring heart rate variability during rest, paced breathing, and upright tilt and was analyzed in time and frequency domains. RESULTS: Cardiovagal testing was performed on 58 participants: 26 controls, 20 non-LD, and 12 LD. After adjustment for visceral fat, time domain analysis showed decreased heart rate variability in patients with LD compared to the other groups (p < .05). The frequency domain analysis showed decreased high-frequency power and increased low- to high-frequency power ratio in the LD group compared to both groups during rest and to non-LD during tilt (p < .05). CONCLUSION: Patients with LD have altered cardiovagal modulation. Patients with LD had lower heart rate variability and higher sympathetic modulation compared to non-LD and controls. These alterations may be prognostic of increased cardiovascular disease morbidity and mortality.

Adult↗