PubMed Health⌕ Search

Biomedical subjects

T Park

Publications and source records attributed to T Park.

At least 37 records · Page 2Linked to original sources
PubMed1998

An approach to categorical data with nonignorable nonresponse.

Log-linear models have been used to adjust for nonresponse when categorical outcomes are subject to nonignorable nonresponse. The log models are fitted to the data in an augmented frequency table in which one index corresponds to whether the subject is a respondent. Park and Brown (1994, Journal of the American Statistical Association 89, 44-52) proposed a pseudo-Bayesian method that has the effect of smoothing the unobserved cell frequencies. Their approach assigns prior observations only to the unobserved cells. Their method was shown to perform better than the maximum likelihood method, which can produce unstable boundary estimates. Generalizing their approach, we propose a new approach that assigns prior observations to both observed and unobserved cells. Through a simulation study, we compare the proposed approach with Park and Brown's and the maximum likelihood approach.

Bayes Theorem↗
PubMed1998

A generalized estimating equations approach for testing ordered group effects with repeated measurements.

In repeated measures studies, we are often interested in comparing group effects in which groups are associated with a certain order relation. We propose testing procedures for ordered group effects using the generalized estimating equations (GEE) approach of Liang and Zeger (1986, Biometrika 73, 13-22). The order-constrained GEE estimators of group effects are approximated by the isotonic regression of the unconstrained GEE estimators. Based on these constrained estimators, we construct test statistics for detecting ordered group effects. The limiting distributions of the test statistics are mixtures of chi-square distributions. A Monte Carlo experiment shows improved performances of the proposed tests over the usual chi-square tests in detecting ordered group effects. The proposed test procedures are illustrated by familial polyposis supplementation trial data.

Adenomatous Polyposis Coli↗
PubMed1997

A test of missing completely at random for longitudinal data with missing observations.

Liang and Zeger proposed a generalized estimating equations approach to the analysis of longitudinal data. Their models assume that missing observations are missing completely at random in the sense of Rubin. However, when this assumption does not hold, their analysis may yield biased results. In this paper, we develop a simple and practical procedure for testing this assumption. The proposed procedure is related to that of Park and Davis.

Aged↗
PubMed1997

Twist-mediated activation of the NK-4 homeobox gene in the visceral mesoderm of Drosophila requires two distinct clusters of E-box regulatory elements.

NK-4, also called msh2 and tinman, encodes a homeodomain transcription factor that is required for the development of the dorsal mesoderm and its derivatives in the Drosophila embryo. Genetic analyses indicate that NK-4 resides downstream of the mesodermal determinant twist, which encodes a basic helix-loop-helix-type transcription factor. However, the regulation of NK-4 by twist remains poorly understood. Using expression assays in cultured cells and transgenic flies, we show that two distinct clusters of E-box regulatory sequences, present upstream of the NK-4 gene, mediate NK-4 expression in the visceral mesoderm. These elements are conserved between the Drosophila melanogaster and Drosophila virilis NK-4 genes and serve as binding sites for Twist (E1 cluster) and NK-4 (E2 cluster) proteins. In cultured cells, Twist and NK-4 binding results in activation of NK-4 gene expression. In transgenic animals, the E1 and E2 clusters are functionally connected, and both elements are required for NK-4 activation in cells of the visceral mesoderm and also for NK-4 repression in cells of the somatic musculature. These results demonstrate that NK-4 is a direct transcriptional target for Twist and its own gene product in visceral mesodermal cells, supporting the idea that twist and NK-4 function in the subdivision of the mesoderm during Drosophila embryogenesis.

Animals↗
PubMed1995

Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families.

Thirty-seven families with four or more cases of breast cancer or breast and ovarian cancer were analyzed for mutations in BRCA1. Twelve different germ-line mutations, four novel and eight previously observed, were detected in 16 families. Five families of Ashkenazi Jewish descent carried the 185delAG mutation and shared the same haplotype at eight polymorphic markers spanning approximately 850 kb at BRCA1. Expressivity of 185delAG in these families varied, from early-onset breast cancer without ovarian cancer. Mutation 4184delTCAA occurred independently in two families. In one family, penetrance was complete, with females developing early-onset breast cancer or ovarian cancer and the male carrier developing prostatic cancer, whereas, in the other family, penetrance was incomplete and only breast cancer occurred, diagnosed at ages 38-81 years. Two novel nonsense mutations led to the loss of mutant BRCA1 transcript in families with 10 and 6 cases of early-onset breast cancer and ovarian cancer. A 665-nt segment of the BRCA1 3'-UTR and 1.3 kb of genomic sequence including the putative promoter region were invariant by single-strand conformation analysis in 13 families without coding-sequence mutations. Overall in our series, BRCA1 mutations have been detected in 26 families: 16 with positive BRCA1 lod scores, 7 with negative lod scores (reflecting multiple sporadic breast cancers), and 3 not tested for linkage. Three other families have positive lod scores for linkage to BRCA2, but 13 families without detected BRCA1 mutations have negative lod scores for both BRCA1 and BRCA2.

Alleles↗
PubMed1994

Activation of the leukocyte plastin gene occurs in most human cancer cells.

Examination of human neoplastic cell lines using reverse transcription-polymerase chain reaction (RT-PCR), Northern blotting, and protein profiling revealed that > 90% of transformed human cell lines surveyed exhibited widely varying degrees of activation of the leukocyte (L)-plastin gene. By contrast, diploid cell types exhibited no evidence of event transient activation of this gene. The low level activation of the L-plastin gene, detectable only by RT-PCR, was confirmed by using the recombinant human L-plastin promoter to select "L-plastin positive" clonal subpopulations from these RT-PCR-positive cell lines. A stable cell line selected by this method exhibited low level constitutive synthesis of L-plastin mRNA and polypeptide. This cell line also exhibited the coinduction of at least three highly abundant new cytoplasmic proteins (M(r) 42,000, 37,000, and 34,000) and reduction in growth rate and saturation density. Most clonal cell lines derived by this selection procedure that activated the L-plastin gene exhibited a crisis stage that led to death of the clonal strain, a phenomenon that could be reproduced by induction of synthesis of recombinant L-plastin from its complementary DNA.

Base Sequence↗
PubMed1993

A comparison of the generalized estimating equation approach with the maximum likelihood approach for repeated measurements.

Liang and Zeger proposed an extension of generalized linear models to the analysis of longitudinal data. Their approach is closely related to quasi-likelihood methods and can handle both normal and non-normal outcome variables such as Poisson or binary outcomes. Their approach, however, has been applied mainly to non-normal outcome variables. This is probably due to the fact that there is a large class of multivariate linear models available for normal outcomes such as growth models and random-effects models. Furthermore, there are many iterative algorithms that yield maximum likelihood estimators (MLEs) of the model parameters. The multivariate linear model approach, based on maximum likelihood (ML) estimation, specifies the joint multivariate normal distribution of outcome variables while the approach of Liang and Zeger, based on the quasi-likelihood, specifies only the marginal distributions. In this paper, I compare the approach of Liang and Zeger and the ML approach for the multivariate normal outcomes. I show that the generalized estimating equation (GEE) reduces to the score equation only when the data do not have missing observations and the correlation is unstructured. In more general cases, however, the GEE estimation yields consistent estimators that may differ from the MLEs. That is, the GEE does not always reduce to the score equation even when the outcome variables are multivariate normal. I compare the small sample properties of the GEE estimators and the MLEs by means of a Monte Carlo simulation study.

Clinical Trials as Topic↗
PubMed1993

Cognitive and behavioral profile of the oculocerebrorenal syndrome of Lowe.

BACKGROUND: The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder characterized by congenital cataracts, cognitive impairment, and renal tubular dysfunction. Significant behavioral difficulties have been reported, but no formal study of intelligence or behavior has been described. METHODS: We surveyed IQ and behavior using archival data and standardized instruments in 47 affected males. RESULTS: Mean IQ was in the moderate mental retardation range (40 < or = IQ < or = 54), with 25% of tested individuals in the normal range (IQ > or = 70). The OCRL population was comparable to a normative population with mental retardation in language, communication, and socialization skills, but lower in independent living skills than means of either populations of individuals with mental retardation or visual impairment. Maladaptive behaviors, particularly stubbornness, temper tantrums, and stereotypic behaviors, were very frequent (> 80%). CONCLUSIONS: The diagnosis of OCRL is compatible with normal intelligence. Maladaptive behaviors significantly interfere with adaptive functions. These behaviors appear to define a characteristic behavioral phenotype in OCRL.

Adolescent↗
PubMed1993

Human plastin genes. Comparative gene structure, chromosome location, and differential expression in normal and neoplastic cells.

Plastins are a family of actin-binding proteins that are conserved throughout eukaryote evolution and expressed in most tissues of higher eukaryotes. In humans, two ubiquitous plastin isoforms (L and T) have been identified. The L isoform is expressed only in hemopoietic cell lineages, while the T isoform has been found in all other normal cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). However, L-plastin has been found in many types of malignant human cells of non-hemopoietic origin suggesting that its expression is induced accompanying tumorigenesis in solid tissues. To learn more about the nature of plastin genes and their potential role in malignancy, the L- and T- plastin genes were cloned and sequenced to characterize their structure and mechanisms of regulation of expression. Each gene was found to be approximately 90 kilobases in size and was composed of 16 exons. All exon-intron junction sequences were identified and shown to conform to the canonical junction sequences. It was evident from their similar structure and coding homology that the two plastin genes have diverged from a common ancestor gene. L- and T-plastin genes were also mapped to chromosomes 13 and X, respectively, using polymerase chain reaction amplification with isoform-specific probes. An expanded survey of normal cell types and 50 tumor cell lines, demonstrated that 68% of carcinomas and 53% of other solid tumors of nonepithelial origin exhibited L-plastin expression, whereas the normal stem cell progenitors did not. Fibrosarcomas (n = 4), ovarian carcinomas (n = 9), breast carcinomas (n = 4), and choriocarcinomas (n = 2) combined exhibited the highest frequency and levels of L-plastin expression (95% frequency). In addition, 4 tumor cell lines that were L-plastin-negative exhibited evidence of defective T-plastin expression increasing the apparent co-incidence of plastin abnormalities associated with human tumorigenesis to 71%. Evidence is presented in support of a trans-activation mechanism for activation of L-plastin synthesis accompanying tumorigenesis. The induction of L-plastin expression accompanying SV40-mediated transformation of human embryonic lung MRC-5 fibroblasts was also confirmed. Finally, we present evidence that fimbrin is a third distinct plastin isoform which is specifically expressed at high levels in the small intestine.

Amino Acid Sequence↗
PubMed1993

Characterization of the human L-plastin gene promoter in normal and neoplastic cells.

Plastins are a family of human actin-binding proteins (isoforms) which are abundantly expressed in all normal replicating mammalian cells. One isoform, L-plastin, is constitutively expressed at high levels in hemopoietic cell types while T-plastin is constitutively expressed in all non-hemopoietic cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). L-plastin is, however, constitutively synthesized in many types of malignant human cells of solid tissues suggesting that its expression is induced during tumorigenesis. The frequency of L-plastin induction in some cancers of the steroid-regulated female reproductive tract (breast, ovary, uterus, and placenta) appears to be especially high (79% in a limited survey). To learn the mechanism of L-plastin gene activation accompanying tumorigenesis, we have begun to characterize the promoter and regulatory elements of the L-plastin gene. Transcription initiation from this promoter was found to occur at multiple sites and as near as 10 base pairs from the 3'-side of the TATAAA box. The promoter and its flanking DNA were cloned and sequenced to identify potential regulatory elements that participate in the induction of the L-plastin gene in neoplastic cells. Examination of upstream sequences revealed the existence of two potential progesterone, one potential estrogen, and four potential Ets-1 responsive elements flanking the promoter. A 315-base pair fragment spanning the TATAAA box and a potential Sp1-binding site exhibited maximum promoter activity using CAT as a reporter while longer promoter fragments extending into upstream flanking sequences spanning the hormone receptor-response elements exhibited reduced promoter activity. An expression vector, pHLPPr-1-neo, was constructed using a 5.1-kilobase pair EcoRI-HindIII fragment of the L-plastin gene that contained the potential upstream regulatory elements, the TATAAA box, and part of the first exon. This promoter could direct the constitutive expression of the reporter beta-galactosidase at high frequency in transfected colonies of transformed cells that express L-plastin constitutively; by contrast, this promoter was virtually inactive in transfected colonies of normal fibroblasts and it exhibited a low frequency of constitutive activation in transfected colonies of in vitro SV40-transformed fibroblasts which did not exhibit L-plastin expression. The utility of this recombinant promoter in determining the mechanism(s) that leads to activation of the L-plastin gene in tumor cells is discussed. The potential significance of regulation of the L-plastin gene by reproductive hormones in cancers arising in hormone-responsive tissues is also discussed.

Base Sequence↗
PubMed1993

A mitochondrial DNA deletion in normally aging and in Alzheimer brain tissue.

By quantitative polymerase chain reaction (PCR) of total cellular DNA, the known 4977 bp deletion in human mitochondrial DNA (mtDNA delta 4977) was not detected in rapidly dividing tissue such as placenta and lymphocytes, nor in brain tissue from fetuses and in frontal cortex from two individuals 24 and 56 years old. However, in frontal cortex from individuals 71-95 years 0.13% deleted/undeleted mtDNA was found, with no significant difference between Alzheimer patients (0.14%) and age-matched controls (0.12%). We hypothesize that the age-related accumulation of this deletion (and other expected deletions) contributes to the down-regulation of adenosine triphosphate (ATP) production in neurons and other non-dividing cells, a fundamental mechanism common to aging and Alzheimer's disease.

Adult↗
PubMed1993

A test of the missing data mechanism for repeated categorical data.

Due to the occurrence of missing observations, longitudinal data are rarely balanced and complete. Weighted least squares analyses described by Grizzle, Starmer, and Koch (1969, Biometrics 25, 489-504) have been developed for the analysis of incomplete longitudinal categorical data [Stanish, Gillings, and Koch (1978, Biometrics 34, 305-317); Woolson and Clarke (1984, Journal of the Royal Statistical Society, Series A 147, 87-99)]. However, all these analyses have assumed that missing observations are missing completely at random in the sense of Rubin (1976, Biometrika 63, 581-592). When the occurrence of missing observations is related to the unobserved response values, these analyses may result in biased results. In this paper, we develop a simple and practical test of the missing mechanism in incomplete repeated categorical data. The proposed test is an extension of the test of Little (1988, Journal of the American Statistical Association 83, 1198-1202) and uses a test criterion given in general form by Wald. The test is illustrated using data from a longitudinal investigation of obesity in school-age children.

Adolescent↗
PubMed1992

Predictors of condom use in sexually active adolescents.

Unprotected sexual intercourse places a substantial number of adolescents at risk for sexually transmitted disease (STD) and human immunodeficiency virus (HIV) infection. While the most effective means of preventing STD/HIV infection among sexually active adolescents is consistent condom use, little is known about the factors that influence their consistent use among adolescents. This study of adolescents (n = 1049, mean age = 16.2 years) found that of the 266 teens who recently became sexually active, only 29% reported using condoms consistently. Consistent condom use was more frequent in males, those with little history of risk behavior and those with stronger intentions to use condoms in the future. Fear and anxiety of HIV, attitudes about risks other than HIV, and other safe behavior intentions were not significantly related to consistent condom use. Although intentions and recent behavior were significantly related, a different group of factors was found to predict intention to use condoms (e.g., perception of condom use by friends, general impulsive attitudes). Identifying and understanding the factors that influence adolescent sexual behavior and intentions is important for developing maximally effective HIV education/prevention programs.

Adolescent↗
PubMed1992

Side effects and the "blindability" of clinical drug trials.

A novel, simple approach to retrospective assessment of "blindability" was applied to data on outpatients in a controlled, double-blind clinical comparison of a putative antidepressant, etoperidone, and placebo. A "blind" evaluator proved capable of discriminating between the active drug and placebo on the basis of reported side effects alone, raising questions about the true blindness of the study.

Ambulatory Care↗
PubMed1991

Relative salience of species maternal calls in neonatal gallinaceous birds: a direct comparison of Japanese quail (Coturnix coturnix japonica) and domestic chickens (Gallus gallus domesticus).

Differential-approach tendencies of individual incubator-hatched chickens and Japanese quail were assayed using one exemplar of each of the species maternal calls in a simultaneous-choice paradigm. Within 24 hr after hatching, the birds received several short periods of exposure to rotating mounts of an adult female chicken and quail, which emitted the species-appropriate call. All birds were then tested with calls alone over the following 2 to 4 days. The test stimuli were played from speakers located behind pressure-sensitive panels so that approach behavior was recorded when a bird pushed against one of the panels. Both the chickens and the quail, as groups, spent significantly more time attempting to approach the exemplar of their own species maternal call, although there was considerable variation in the magnitude of the approach difference among individuals within each species. Sources of variation in preference scores are analyzed, and a simulation is used to interpret individual differences in response scores. This type of preference test is useful for a number of applications, notably for studying the behavior of quail-chick nervous system chimeras.

Age Factors↗
PubMed1991

Traumatic cervical Brown-Sequard and Brown-Sequard-plus syndromes: the spectrum of presentations and outcomes.

Brown-Sequard syndrome (BSS) and Brown-Sequard-plus syndrome (BSPS) are characterised by asymmetrical paresis with hypalgesia more marked on the less paretic side. This study examined the clinical features of 38 patients (30 males and 8 females; mean age = 32 years) with traumatic cervical BSS or BSPS who underwent comprehensive inpatient rehabilitation. Twenty two injuries were caused by road traffic accidents, 8 by penetrating injuries, 5 by diving injuries, and 3 by other causes. After an average of 35 days in acute care and 79 days in rehabilitation, 37 patients had increased muscle strength, all 38 patients improved functional abilities, 29 patients walked independently, 34 had spontaneous bladder emptying, 36 were discharged home, and 14 were employed. Statistically significant increases (p less than 0.001) were made in modified Barthel index functional scores between admission and discharge. Patients with BSPS had a better prognosis than did those with 'pure' BSS. Patients with predominant upper limb weakness had more favourable outcomes than did those with predominant lower limb weakness. Few other potentially predictive demographic, injury, or neurological factors were associated with functional outcome. Patients with BSS or BSPS generally have a good prognosis for neurological and functional improvement.

Activities of Daily Living↗
PubMed1991

Dietary acid and alkali loading do not alter taurine uptake by renal proximal tubule brush border membrane vesicles in kittens.

Kittens adapted to a purified control diet containing 43.5% soy protein plus 0.15% taurine were randomly divided into three groups: control, acid-loaded or alkali-loaded. For dietary acid or alkali loadings, 2% NH4Cl or 0.87% NaHCO3 plus 0.87% KHCO3 were added to the control diet. Acid-loaded, control and alkali-loaded kittens had venous blood pH of 7.33 +/- 0.01, 7.37 +/- 0.02 and 7.39 +/- 0.02, and urine pH of 5.5 +/- 0.1, 7.2 +/- 0.1 and 8.1 +/- 0.1, respectively. After 6 wk of the dietary treatment, the plasma taurine concentrations of acid-loaded, control and alkali-loaded kittens were 74 +/- 4, 77 +/- 7 and 87 +/- 8 mumol/L (P greater than 0.05) respectively. Compared with the control group, dietary acid or alkali loading did not significantly change the taurine uptake by brush border membrane vesicles (BBMV) when BBMV were at the same in vitro pH (7.35). However, when the pH of the medium was changed to 8.0 for the alkali-loaded group or to 5.5 for the acid-loaded group, the initial taurine uptake was significantly elevated (55%) or decreased (31%) (P less than 0.05), respectively, compared with the values for the control group at pH 7.35. When BBMV prepared from the same group were tested at different pH levels (8.0 vs. 7.35 vs. 5.5), the initial uptake significantly increased (30%) at pH 8.0 and decreased (37%) at pH 5.5 compared with that observed at pH 7.35 (P less than 0.05), regardless of the acidity of the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonium Chloride↗