Biomedical subjects
Publications and source records attributed to S Lai.
A tandem chain extension-aldol reaction was developed in which beta-keto esters are transformed to alpha-substituted-gamma-keto esters in an efficient zinc-mediated, one-pot reaction. The diastereoselectivity of the reaction ranged from good to excellent with syn stereochemistry observed for beta-keto ester and amide substrates and anti-stereochemistry observed for a beta-keto imide. [reaction: see text]
OBJECTIVE: To assess whether initiation of highly active antiretroviral therapy (HAART) is associated with a subsequent resumption of sexual and drug use risk behaviors. METHODS: Within an ongoing prospective study of HIV-seropositive injection drug users (IDUs), a subsample with at least one CD4 cell count < 500 x 106 cells/l after 1996 (when HAART became available) and three consecutive visits were selected for analysis. Patients underwent semi-annual interviews for risk behaviors and reports of medication use. Data from visits immediately prior to and following initiation of HAART for the treated group, and from consecutive visits for the eligible but untreated group were compared using linear growth curve analysis. RESULTS: Of 316 eligible HIV-seropositive IDUs, 133 reported HAART use during the study period; 95% were African American, 76% were male, and median age at enrollment was 34 years. The proportion who reported any sexual activity increased over time from 55 to 61% for the HAART-treated group, but decreased from 67 to 63% in the untreated group (P = 0.03); the respective values for unprotected sex were 18 versus 20% and 36 versus 28% (P = 0.06). In both treated and untreated groups, the proportion injecting drugs declined (P = 0.04), whereas the proportion reporting needle sharing decreased marginally (P = 0.11). However, trends in use of shooting galleries between the groups differed (P = 0.04) increasing slightly from 2.3 to 3% in the treated group while decreasing from 12 to 5% in the untreated group. CONCLUSION: In persons treated with HAART, self-report of high-risk behaviors remained stable or showed some increase. Persons initiating HAART should be counselled to refrain from high-risk behaviors.
A fully integrated, miniaturized analysis system for ions based on a centrifugal microfluidics platform and ion-selective optode membranes is described. The microfluidic architecture is composed of channels, five solution reservoirs, a measuring chamber, and a waste reservoir manufactured onto a disk-shaped substrate of poly(methyl methacrylate). Ion-selective optode membranes, composed of plasticized poly(vinyl chloride) impregnated with an ionophore, a proton chromoionophore, and a lipophilic anionic additive, were cast, with a spin-on device, onto a support layer and then immobilized on the disk. Fluid propulsion is achieved by the centrifugal force that results from spinning the disk, while a system of valves is built onto the disk to control flow. These valves operate based on fluid properties and fluid/substrate interactions and are controlled by the angular frequency of rotation. With this system, we have been able to deliver calibrant solutions, washing buffers, or "test" solutions to the measuring chamber where the optode membrane is located. An analysis system based on a potassium-selective optode has been characterized. Results indicate that optodes immobilized on the platform demonstrate theoretical responses in an absorbance mode of measurement. Samples of unknown concentration can be quantified to within 3% error by fitting the response function for a given optode membrane using an acid (for measuring the signal for a fully protonated chromoionophore), a base (for fully deprotonated chromoionophore), and two standard solutions. Further, the ability to measure ion concentrations by employing one standard solution in conjunction with acid and base and with two standards alone were studied to delineate whether the current architecture could be simplified. Finally, the efficacy of incorporating washing steps into the calibration protocol was investigated.
A prospective cohort study of 121 HIV-1-positive homosexual men was conducted in Miami, Florida, U.S.A. to evaluate the associations between plasma zinc and copper levels and mortality. Plasma zinc and copper levels were measured at baseline and then at semiannual visits. Zinc inadequacy and copper inadequacy were defined as plasma zinc levels <75 (microg/dl) and plasma copper levels <85 (microg/dl), respectively. HIV-1-related deaths were confirmed by review of death certificates. Cox proportional hazards regression models with time-dependent covariates were used to estimate the relative risks of zinc and copper inadequacy on mortality. Over the average course of the 3.3-year follow-up, 19 participants (16%) died of HIV-1-related causes. After adjustment for potential confounders, including low CD4+ cell counts and antiretroviral therapy, zinc inadequacy and copper:zinc ratio >1 (i.e., plasma copper level greater than plasma zinc level) were associated with increased mortality (relative risks [RRs]; 95% confidence intervals [CIs], 4.98, 1.30-19.00 and 8.28, 1.03-66.58, respectively). A negative association was also observed between plasma zinc levels and mortality (RR 0.94; 95% CI, 0.91-0.98). Plasma levels of copper were not significantly associated with mortality. These results suggest that plasma zinc inadequacy or the plasma copper:zinc ratio may be useful predictors of survival in HIV-1 infection. The latter appears to be a stronger predictor.
Guangxi Province, China recently experienced an outbreak of HIV-1 infection among heroin users. We studied HIV-1 incidence rates and associated risk factors for HIV-1 infection among heroin users residing in Pingxiang City. A total of 318 heroin users were followed from February 1998 through January 1999 (median follow-up: 8.1 months). Of these, 130 were prospectively followed from January through September 1999 (median follow-up: 8.3 months). HIV-1 and hepatitis C virus (HCV) incidence rates for each period were calculated. A generalized estimating equation approach was implemented to identify independent risk factors associated with HIV-1 infection across both periods. Among 318 study participants, 97.2% were men. The median age was 22 years. Approximately 60% reported sharing needles. HIV-1 prevalence at baseline was 15.4%. During the first follow-up period, HIV-1 incidence was 2.38 per 100 person years (py), and HCV incidence was 26.8 per 100 py. During the second follow-up period, HIV-1 incidence was 6.86 per 100 py, and HCV incidence was 28.9 per 100 py. After controlling for age and other factors, HCV seropositivity, history of sexually transmitted diseases, and sharing needles were independently associated with HIV-1 infection. These data suggest that HIV-1 incidence was rising over time in Pingxiang City, Guangxi Province. The high incidence of HCV heightens the importance of enhanced prevention programs to reduce injection and needle sharing among heroin users.
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We have previously shown that event-related functional magnetic resonance imaging (ER-fMRI) may be used to record responses to the rapid, interleaved presentation of stimuli in the three-stimulus oddball task. The present study examined the sensitivity of ER-fMRI responses to variations in the range of inter-stimulus intervals (ISIs, calculated as the time from the offset of one stimulus to the onset of the next stimulus) and the type of behavioral response task used. ISIs were varied between a wide ISI range (550-2,050 msec) and a narrow ISI range (800-1,200 msec), while maintaining a similar mean ISI (approximately 1 stimulus per sec) between experiments. The response task was varied between button press and subvocal target counting. Gradient echo, echo planar images were acquired for each of three experiments (wide ISI with button press, narrow ISI with button press, and wide-ISI with counting) in five subjects. Target stimuli generated increased fMRI signal in a wide range of brain regions. The use of a narrow ISI range generated a greater volume of subcortical activity and a reduced volume of cortical activity relative to a wide ISI range. The counting task generated a larger amplitude and longer lasting evoked response in brain regions that responded during all three experiments. Rare distractor stimuli evoked fMRI signal change primarily in orbitofrontal, ventral-medial prefrontal and superior parietal cortex. These results illustrate that although ER-fMRI is relatively insensitive as a technique to small variations in the timing of stimulus-evoked responses, it is remarkably sensitive to consequences such variations have for the topographic location and amplitude of neural responses to stimuli.
Candidate brain regions constituting a neural network for preattentive phonetic perception were identified with fMRI and multivariate multiple regression of imaging data. Stimuli contrasted along speech/nonspeech, acoustic, or phonetic complexity (three levels each) and natural/synthetic dimensions. Seven distributed brain regions' activity correlated with speech and speech complexity dimensions, including five left-sided foci [posterior superior temporal gyrus (STG), angular gyrus, ventral occipitotemporal cortex, inferior/posterior supramarginal gyrus, and middle frontal gyrus (MFG)] and two right-sided foci (posterior STG and anterior insula). Only the left MFG discriminated natural and synthetic speech. The data also supported a parallel rather than serial model of auditory speech and nonspeech perception.
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OBJECTIVES: To examine the geographic variation in the use of radiation to treat nonmetastatic prostate cancer and to identify factors that explain the variation in the United States. METHODS: This study was based on data from the nine geographic regions of the Surveillance, Epidemiology, and End Results Program for 1983 through 1996. Patients with localized or regional prostate cancer who did not undergo surgical treatment were included in the analysis. Logistic regression analysis was used to investigate the influence of geographic and demographic factors on the use of radiation. The squared multiple correlation coefficient R(2) was used to measure the proportion of variation in the selection of radiation explained by each factor of interest. RESULTS: Compared with San Francisco, the adjusted odds ratios for 6 of the 8 geographic areas had highly significant P values, suggesting the use of radiation therapy varies from region to region. However, geographic location only explained less than 3% of the total variation in the use of radiation. The geographic location explained a much higher proportion of variation in the youngest (younger than 55 years) and the oldest (80 years old or older) groups. Overall, age was the most important factor that influenced the use of radiation. CONCLUSIONS: The finding that geographic location explains a significant proportion of the variation in the use of radiation in the youngest and oldest age groups demonstrates the outcome of longstanding controversies in the nonsurgical treatment of prostate cancer. Documenting the impact of the interaction of age and geographic location on the treatment approaches provides for better understanding of the impact of patients and physicians making clinical decisions in the management of nonmetastatic prostate cancer.
OBJECTIVES: To examine whether the survival (both overall and disease-specific) of patients who underwent radical prostatectomy varies from region to region in the United States. Previous reports have documented a geographic variation in the use of radical prostatectomy. METHODS: This study was based on the data from nine geographic regions of the Surveillance, Epidemiology, and End Results Program (SEER) for 1983 through 1992. Patients with localized prostate cancer who underwent radical prostatectomy were included in the analysis. A proportional hazards model was used to investigate whether geographic variation is associated with both overall and disease-specific survival. RESULTS: From 1983 through 1992, the SEER Program collected information from nine geographic regions on 66,293 patients with localized prostate cancer (mean age 71.8 +/- 8.4 years), who had SEER grade codes of 1, 2, or 3. Of these patients, 11,429 (mean age 65.3 +/- 6.5 years) underwent radical prostatectomy and lymph node dissection. Cox's proportional hazards analyses revealed that the impact of geographic location on both overall and disease-specific survival in patients who underwent radical prostatectomy was not statistically significant. CONCLUSIONS: The results of this study indicate that the survival (both overall and disease-specific) of patients with localized prostate cancer who underwent radical prostatectomy is not influenced by geographic location, suggesting that their survival is relatively uniform across the geographic regions in the United States.
OBJECTIVES: The study compared the prognostic significance of myocardial perfusion single-photon emission computed tomography (SPECT) (MPS) in patients early and late after coronary artery bypass graft surgery (CABG). BACKGROUND: The long-term effectiveness of CABG is limited by graft stenosis. The greatest incidence of graft occlusion occurs between five and eight years after surgery. However, little is known regarding the appropriate time to stress patients post-CABG with respect to risk stratification. METHODS: We identified 1,765 patients, who underwent MPS 7.1 +/- 5.0 years post-CABG. All patients underwent rest T1-201/stress Tc-99m sestamibi MPS and were followed up > or =1 year after testing. Patients with early CABG or PTCA (<60 days after MPS) were censored. The prognostic population consisted of 1,544 patients. A semiquantitative visual analysis employing a 20-segment model was used to define summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), and the number of nonreversible segments (NRS). RESULTS: During follow-up, 53 cardiac deaths (CD) occurred. There was a significant increase in annual CD rates as a function of SSS. A multivariate analysis identified age, ischemia (SDS), and infarct size (NRS) as independent predictors of CD. Nuclear variables added incremental value to prescan information. The annual CD rate was relatively low (1.3%) in patients < or =5 years post-CABG. In this subgroup only age and infarct size (NRS) were predictive of CD. CONCLUSION: MPS is strongly predictive of subsequent CD in post-CABG patients and adds incremental value over clinical and treadmill test information. Our data suggest that symptomatic patients < or =5 years and all patients >5 years post-CABG may benefit from testing.
Asian countries adjacent to the Golden Triangle and their neighbors have witnessed an evolution in "drug abuse" from traditional opium smoking to heroin eating, smoking, and finally heroin injection. A recent study of 630 heroin users was conducted in China's Yunnan Province, located close to the Golden Triangle. Data collected between August 1997 and February 1998 indicate injecting heroin users, in comparison to noninjectors, were more likely to have used drugs for a longer period of time, and to use drugs more frequently everyday. Other major differences existed between urban and rural subjects, especially highlighting differences between men and women. Women comprised a much higher proportion of urban subjects than rural subjects. Rural injectors were much more likely to be male, but urban injectors were almost evenly split between men and women. The emerging epidemic of heroin use in China and the continuing substance abuse problem in the United States provide an opportunity for collaborative research of mutual benefit.
p73, a recently identified gene, maps to chromosome region 1p36.3, which is frequently deleted in a variety of solid tumors. Although the gene shares sequence and functional homologies with p53, its suppressor function has not been proven. We investigated for the first time the genetic and expression status of the p73 gene and analyzed its flanking microsatellite loci on chromosome 1p36.3 in 67 primary oral and laryngeal squamous cell carcinomas to determine their association with these tumors. Our results reveal two missense mutations at codons 469 and 477 and a silent mutation at codon 349 in the C-terminal domain. Site-directed mutagenesis of p73 cDNA with these mutations and a p21 transactivation assay failed to show any significant functional consequences of these mutations. Microsatellite analysis of the flanking loci of p73 in region 1p36 showed overall alterations (loss of heterozygosity and instability) frequency of 39%, 16% at the proximal marker and 46% at the distal markers. Of the 21 cases for which we did protein expression analyses, 11 tumors had a >2-fold variation compared with matching histologically normal mucosa. Our study shows that: (i) intragenic alterations in this gene are rare and lack functional significance; (ii) its variable expression argues against a tumor suppressor function; (iii) this gene plays a minor role in head and neck squamous carcinoma; (iv) a distal site to this gene on 1p36 may harbor another suppressor gene.
Healthy physiological systems exhibit marked signal variability and complexity, whereas diseased systems generally show a loss of variability, decreased complexity ("decomplexification"), and increased regularity. The goal of this study was to evaluate the uncoupling and recoupling phenomenon in children with septic shock by observing serial changes in heart rate variability metrics. Data were collected from 7 children with septic shock by using the computer system in the Complex Systems Laboratory at Oregon Health Sciences University. Heart rate time series were constructed and analyzed by using the Hales Research System at intervals of 6 h during pediatric intensive care unit (PICU) hospitalization. These power spectral values were then plotted vs. time. Six of seven patients showed an increase over time in low-frequency heart rate power and the low-/high-frequency ratio, whereas high-frequency heart rate power decreased. We also compared the change in mean heart rate, heart rate standard deviation, and power spectral values during the first 24 h of PICU hospitalization vs. the remainder of the PICU stay (for the 5 patients with a PICU length of stay > 48 h). Compared to the initial 24 h in the PICU, low-frequency power and the low-/high-frequency ratio increased, whereas high-frequency power decreased over the course of the illness. This report shows the potential value of monitoring the uncoupling and recoupling phenomenon in patients with septic shock. Our results are in agreement with other investigators who report evidence of decomplexification both in experimental models of sepsis and in clinical studies and provide direction for further work.
In the experimental studies designed to evaluate the effects of different factors on the biomechanical properties of bone, careful selection of rats and the scientific indices is very important. The aim of this paper is to recommend some essential methods for testing and calculating the biomechanical properties of rat bone such as tension, compression, bending and torsion.
OBJECTIVE: To investigate the distribution of apolipoprotein E (apoE) genotype of patients with Alzheimer's disease (AD) in the population aged 75 and older in Guangzhou and to determine whether there was an association between AD and apoE epsilon4 allele. METHODS: A systematic cluster sampling design, two-stage screening and field evaluations were used in a cross-sectional population-based study. Three thousand eight handred and twenty-five subjects aged 75 and above in Liwan district of Guangzhou were interviewed. Blood samples were collected from 110 cases and 518 normal controls. The criteria of DSM-III-R and NINCDS-ADRDA were used for clinical diagnosis of probable AD. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to determine apoE genotypes. RESULTS: There were 190 cases diagnosed as sporadic AD from this sample. The frequencies of the three apoE alleles were detected as follows: epsilon2 = 0.100, epsilon3 = 0.832, epsilon4 = 0.068 in AD patients; epsilon2 = 0.092, epsilon3 = 0.843, epsilon4 = 0.065 in normal controls. The frequencies of apoE genotype and allele in the AD patients were not significantly different from that in normal subjects (P > 0.05). CONCLUSION: No association between sporadic AD and apoE epsilon4 allele was found among the population aged 75 and above in Liwan district of Guangzhou.
Stereospecifically (3)H-labeled substrates are useful tools in studying the mechanism of hydrogen abstractions involved in the oxygenation of polyunsaturated fatty acids. Here, we describe modified methods for the synthesis of arachidonic acids labeled with a single chiral tritium on the methylene groups at carbons 10 or 13. The appropriate starting material is a ketooctadecanoic acid which is prepared from an unsaturated C18 fatty acid precursor or by total synthesis. The (3)H label is introduced by NaB(3)H(4) reduction and the resulting tritiated hydroxy fatty acid then is tosylated, separated into the enantiomers by chiral phase HPLC, and subsequently transformed into stearic acids. A variety of stereospecifically labeled unsaturated fatty acids are obtained using literature methods of microbial transformation with the fungus Saprolegnia parasitica. Two applications are described: (i) In incubations of [10S-(3)H]- and [10R-(3)H]arachidonic acids in human psoriatic scales we show that a 12R-lipoxygenase accounts not only for synthesis of the major product 12R-HETE, but it contributes also, through subsequent isomerization, to the minor amounts of 12S-HETE. (ii) The [10R-(3)H]- and [10S-(3)H]arachidonic acids were also used to demonstrate that prostaglandin ring formation by cyclooxygenases does not involve carbocation formation at C-10 of arachidonic acid as was hypothesized recently.