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PubMed2006

Access to pediatric liver transplantation: does regional variation play a role?

The purpose of this study was to assess regional variability in access to pediatric liver transplantation. The study population included all pediatric patients (age less than 18 years) listed for liver transplantation in the United Network for Organ Sharing (UNOS) database between 1988 and 2004. The effect of region on waiting list survival, the proportion of patients transplanted, and the proportion of patients remaining on the list was determined using Kaplan-Meier and Cox proportional hazard methods. The proportion of technical variant grafts used was compared between regions using chi-square analysis. Kaplan-Meier analyses showed significant effects of region on survival on the waiting list, transplantation, and remaining on the list (all log-rank P < 0.001). Cox proportional hazard models demonstrated that region, urgency status, and listing period exerted independent effects on survival on the waiting list, transplantation, and remaining on the list (all model P < 0.01). Regional variation existed with regard to donor type (P < 0.001). Similar to adults, pediatric survival on the waiting list, the proportion of patients transplanted, and the proportion of patients remaining on the waiting list vary considerably within the 11 U.S. regions. Organ procurement organization specific effects and regional differences in utilization of deceased donor split and living donor organs may contribute to this variability.

Adolescent↗

PubMed2006

Unequal placental sharing and birth weight discordance in monochorionic diamniotic twins.

OBJECTIVE: The purpose of this study was to define the association between unequal placental sharing and birth weight discordance in monochorionic/diamniotic twin pregnancies. STUDY DESIGN: The study comprised a prospective cohort of monochorionic/diamniotic twin pregnancies who were delivered in Kaiser Permanente-Northern California, 1997-2003. Dye injection studies of fresh postpartum placentas were performed. Placental sharing, cord insertion combinations, vascular anastomoses, gestational age, and birth weights were recorded. Statistical comparisons of birth weight and gestational age were made with the Student t test. Rates of birth weight discordance were compared with the chi-square test. Multivariate logistic regression models analyzed the relationship between variables of interest. RESULTS: Mean birth weights for larger and smaller twins were 2400 g and 2109 g, respectively. Twenty-two percent of the monochorionic/diamniotic twin pairs had birth weight discordance > or = 20%, and 8% of these pairs had twin-twin transfusion syndrome. Monochorionic/diamniotic twin pairs with unequal placental sharing had a 9.8 times greater likelihood of birth weight discordance (95% CI, 5.4-17.9) as compared with those pairs with equal placental sharing. CONCLUSION: Unequal placental sharing is a significant risk factor for birth weight discordance in monochorionic/diamniotic twins. Antenatal diagnosis of unequal placental sharing would enable improved counseling in the setting of monochorionic/diamniotic twins.

Amnion↗

PubMed1996

Evaluation of a new general primer pair for rapid detection and differentiation of HSV-1, HSV-2, and VZV by polymerase chain reaction.

The polymerase chain reaction (PCR) enables rapid and sensitive detection of VZV and HSV DNA and its efficiency depends mainly on the choice of the primers. Primers should hybridize to conserved DNA sequences within the viral genomes in order to avoid unreliable amplification due to DNA sequence variation between different strains. The aim of the study was to design and to evaluate a general primer pair which permits fast and reliable detection of HSV and VZV. The genes UL 15 of HSV and UL 42 of VZV share the highest degree of homology within the two genomes. We designed a primer pair (GPHV-RU) which hybridizes to these genes. The genetic variability of amplified sequences from clinical specimens was analyzed by restriction enzyme cleavage analysis and by temperature gradient SSCP analysis (TG-SSCP). PCR with GPHV-RU amplified viral sequences from all analyzed specimens (25 x VZV, 10 x HSV-1, 5 x HSV-2) obtained from patients with clinical evidence of HSV or VZV infection. Restriction enzyme cleavage analysis with Hpa II further permitted reliable distinction between VZV, HSV-1, and HSV-2. Analysis of the heterogeneity of the amplified sequences by restriction enzyme cleavage and by TG-SSCP demonstrated no variability between the analyzed clinical specimens of VZ and of HSV-2 and only one differing TG-SSCP-pattern within the HSV-1 isolates. The results suggest that detection of HSV and VZV using the new primer pair GPHV-RU should give reliable results as the amplified sequences show little genetic variability within clinical isolates of HSV-1/2 and VZV.

DNA Primers↗

PubMed1999

First cytogenetic study of a recurrent familial chordoma of the clivus.

Two recurrences of a familial clivus chordoma, arisen from a patient who developed the primary tumor at age of 8 years, were investigated by cytogenetic and the fluorescence in situ hybridization (FISH) approach. Of the patient's 3 daughters, 2 developed, respectively, a clivus chordoma and an astrocytoma in infancy, a familial aggregation highly suggestive of a genetic background. After a 31-year hiatus, 2 tumor recurrences, developed over 17 months, were removed surgically. Both were hypo- or nearly diploid, and had a pronounced karyotypic heterogeneity with clonal and non-clonal rearrangements affecting several chromosomes. The same rearrangement, a dic(1;9)(p36.1;p21), was shared in both tumor specimens and, in 90% of the cells, chromosome 1p appeared to be involved in unbalanced translocations with different chromosomes, leading to variable losses of 1p. Previous cytogenetic data concerning chordoma are limited to 10 sporadic tumors with an abnormal karyotype; although no tumor-specific rearrangements have been identified, chromosome 1p appears to be involved frequently.

Adolescent↗

PubMed1990

A two-step method for understanding and fitting growth curve models.

With data from a repeated measures design, analysts often overlook growth curve analysis based on the Potthoff-Roy model. The reluctance to perform a growth analysis may result partially from unfamiliarity with the technique, and partially from the lack of readily available computational programs to fit the models. Although growth curve analysis has traditionally appeared as a special technique in multivariate analysis, one can fit the models with the use of two simple ideas: transformation of variables, and weighted least squares (WLS). When presented in this manner, growth models are a natural extension of univariate repeated measures models. Growth curve analyses share with univariate analyses the common objective to limit estimation to a parsimonious set of parameters that characterize the response profiles. One can readily fit models with commonly available software. The two-step methodology also allows the fit of more general growth models that are appropriate when groups have different shape profiles. Two examples illustrate this approach to growth curve analysis.

Animals↗

PubMed1996

Differential expression of the EF-hand calcium-binding protein calsensin in the central nervous system of hirudinid leeches.

By immunocytochemistry the distribution and developmental expression of the small EF-hand calcium-binding protein calsensin in the peripheral (PNS) and central nervous system (CNS) of the three hirudinid leech species Haemopis, Hirudo, and Macrobdella was compared. Labeling with calsensin-specific antibodies demonstrated that there was a pronounced difference in the distribution of calsensin immunoreactivity in the CNS of these leeches. In Haemopis more than 70 neurons were labeled, whereas the number in Hirudo was 51 and in Macrobdella only 8. Furthermore, the expression of calsensin in identified cells common to all three leech species also differed. Immunoblot analysis indicated that this variability was not likely to be due to multiple proteins or isoforms being recognized by the calsensin antibody. Labeling of embryos in various stages of development shows that the ontogeny of calsensin expression in the CNS is a gradual process with some neurons expressing calsensin immediately after completion of neurogenesis, about one-third of the way through embryogenesis, and others expressing calsensin only postembryonically. In contrast to the variability in the pattern and temporal expression by CNS neurons, the early embryonic calsensin expression in a small subgroup of sensillar PNS neurons was a shared feature by all three leech species. These findings suggest that calsensin may have different functional properties in CNS and PNS neurons.

Animals↗

PubMed1992

Irregular ventricular tachycardia: a possible manifestation of longitudinal dissociation within the reentry pathway.

Sustained monomorphic ventricular tachycardia is usually regular; that is, it is associated with constant R-R intervals. In several cases, however, the cycles of ventricular tachycardia are more or less variable. Fifty-four cases of sustained monomorphic ventricular tachycardia were evaluated in order to assess whether tachycardia was regular. Nine cases were defined as irregular (i.e., the R-R cycles varied by more than 40 msec throughout a 1-minute recording). In five cases tachycardia was "regularly irregular," since the R-R cycles could be divided into two separate groups: the group of long cycles and that of short cycles. In these cases the variability manifested according to a defined and constant pattern: bigeminal pattern (alternation of short and long cycles), trigeminal pattern (two short cycles followed by a long cycle), and so on. The regular variability of tachycardia cycle length suggests one of the following possibilities. (1) There are two alternative circuits (a short circuit and a long circuit) that share the same exit pathway. Whenever the reciprocating impulse runs through the short circuit, the R-R cycle is short; but if a block in the short circuit occurs, the impulse runs through the long circuit, resulting in a long R-R cycle. (2) There is a longitudinal dissociation within the reentry circuit; two separate pathways with different inherent conduction velocities are present. When the impulse runs through the fast pathway, the R-R cycle is short; whereas when a block in the fast pathway occurs, the impulse traverses the slow pathway, resulting in a long R-R cycle.

Electrocardiography↗

PubMed1992

Familial breast and ovarian cancers.

Breast and ovarian cancer develop independently of each other but share some genetic commonality. Definition and identification of hereditary breast cancer are very complex. Ovarian cancer can be inherited in an autosomal dominant pattern with variable gene penetrance, a site specific hereditary pattern, or a pattern of tumor combinations. Medical management of high risk individuals, follow-up, screening, and counseling needs are important issues to the woman and other family members.

Breast Neoplasms↗

PubMed2005

Functional polymorphisms of HSPA5: possible association with bipolar disorder.

Altered endoplasmic reticulum stress (ER) response signaling is suggested in bipolar disorder. Previously, we preliminarily reported the genetic association of HSPA5 (GRP78/BiP) with bipolar disorder. Here, we extended our analysis by increasing the number of Japanese case-control samples and NIMH Genetics Initiative bipolar trio samples (NIMH trios), and also analyzed schizophrenia samples. In Japanese, nominally significant association of one haplotype was observed in extended samples of bipolar disorder but not in schizophrenia. In NIMH trios, no association was found in total samples. However, an exploratory analysis suggested that the other haplotype was significantly over-transmitted to probands only from the paternal side. The associated haplotype in Japanese or NIMH pedigrees shared three common polymorphisms in the promotor, which was found to alter promotor activity. These findings suggested promotor polymorphisms of HSPA5 may affect the interindividual variability of ER stress response and may confer a genetic risk factor for bipolar disorder.

Adult↗

PubMed2004

The semantic organisation of proper nouns: the case of people and brand names.

We describe the performance of a patient (AZ) with a semantic refractory access disorder on a series of experiments probing comprehension of two broad proper noun categories, namely person names and brand names. By inducing and manipulating the semantic relatedness effects which are commonly observed in semantic refractory access patients, we demonstrate that famous person knowledge is primarily organised by occupation, whilst knowledge of brands is organised by product type. For instance, we show that AZ has significantly greater difficulty identifying a famous person from among distractor personalities who have the same occupation (e.g. composers: Beethoven, Mozart, Handel, and Bach) than those who have different occupations (e.g. Beethoven, Picasso, Shakespeare, and Jefferson). We also show that such semantic relatedness effects do not occur when stimuli are grouped by another variable such as nationality. We argue that these semantic distance effects reflect the greater build-up of refractoriness among concepts which are supported by shared neural circuitry. In psychological space, it seems natural that these individuals should be classified in this way. The strength of our findings lie in the fact that this organisation of psychological space is mirrored by neural organisation. Thus, we report a previously undocumented degree of fine-grain organisation within conceptual knowledge of these classes of proper nouns. We also interpret our data as providing the strongest empirical support to date for the semantic module of cognitive models of person recognition.

Aged↗

PubMed1985

The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family.

The surface glycoproteins T4 and T8 define different functional subsets of T lymphocytes and may act as recognition molecules mediating appropriate interactions between the T cell and its target. Previously we employed gene transfer and subtractive hybridization to isolate a T8 cDNA; now we have isolated and sequenced a cDNA clone encoding the T4 molecule. The deduced protein sequence reveals that T4 is an integral membrane protein that shares significant amino acid and structural homologies with members of the immunoglobulin supergene family. The overall structure of T4 consists of an N-terminal variable (V)-like domain, a joining (J)-like region, a third extracellular domain, a membrane-spanning region homologous to class II MHC beta-chains, and a highly charged cytoplasmic domain. Comparison of the protein sequences deduced from the T4 and T8 cDNAs reveals structural similarities consistent with their postulated role as recognition molecules, as well as differences suggesting that the two proteins recognize different structures on the target cell.

Amino Acid Sequence↗

PubMed1997

Conservation of a putative inhibitory domain in the GAL4 family members.

The GAL4 family members are fungal transcriptional activators composed of several functional domains: a characteristic cysteine-rich DNA-binding domain common to all members, a dimerization domain, various transactivation domains generally exhibiting a high acidic content and a highly variable central region supposed to be involved in regulation and in effector recognition. We report here that the central region of the GAL4 family members share eight conserved motifs embedded in a large functional domain of 225 up to 405 residues. This domain may also be present in four proteins belonging to another family of transcriptional activators sharing a C2H2-type zinc finger. Analysis of the biochemical data available on the well-studied GAL4 protein suggests that this domain may be involved in the regulation of the activity of the protein, particularly in an inhibitory function. This hypothesis is further supported by deletion and site-directed mutagenesis experiments on other GAL4 family members. The mean secondary structure prediction performed on the eight motifs strongly suggests that the inhibitory activity may be mediated by hydrophobic interactions linked to the presence of amphipathic alpha-helices.

Amino Acid Sequence↗

PubMed2005

Contributions of parental alcoholism, prenatal substance exposure, and genetic transmission to child ADHD risk: a female twin study.

BACKGROUND: Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously. METHOD: Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975-1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk. RESULTS: ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences. CONCLUSIONS: Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.

Adolescent↗

PubMed2002

Potential use of chemical cues for colony-mate recognition in the big brown bat, Eptesicus fuscus.

Bats should benefit from recognition of their roost-mates when colonies form stable social units that persist over time. We used Y-maze experiments and gas chromatography-olfactometry (GC-O) to evaluate whether female big brown bats Eptesicus fuscus (Chiroptera: Vespertilionidae) use chemical cues to distinguish among conspecifics. In dual-choice Y-maze experiments, females chose the scent of another female from their own roost over a conspecific female from a different roost in a majority of trials. Analysis of total body odors using GC-O suggests that individuals from a given colony may share a more common odor signature with roost-mates than with non-roost-mate conspecifics. Using four principle components derived from 15 odor variables, discriminant function analysis correctly assigned most individuals to the correct colony.

Animal Communication↗

PubMed1992

Changes in the marital relationship after the first baby is born: predicting the impact of expectancy disconfirmation.

A longitudinal study of 50 couples during the transition to first parenthood examined how failure to confirm expectations regarding the sharing of child-care and housekeeping responsibilities influenced postpartum reports of marital satisfaction. On the basis of recent theories of expectancy confirmation processes, 5 variables representing strength and importance were identified as possible moderators. As predicted, disconfirmation of stronger and more important expectations generally led to more negative reports about the marriage. Surprisingly, some subsets of wives showed opposite reactions; less negative feelings when they were doing more than they expected. These findings were interpreted in terms of personal and role traditionality influencing the valence of the reactions to expectancy disconfirmation.

Adaptation, Psychological↗

PubMed1999

Conserved nucleotide differences and subfamily structure of porcine short interspersed elements.

Interspersed elements are ubiquitous in the genomes of higher eukaryotes and account for over a third of the genomic DNA (Smit 1996). In swine the short interspersed elements, SINEs or PREs (porcine repetitive elements), have been found in a number of introns and 3' untranslated regions of different genes. However, compared to human Alu repeats the number of available PRE DNA sequences is still limited. In this study we have compared 85 PREs selected from DNA sequence database entries. The PREs were aligned and for each nucleotide position the relative frequencies of the four bases were calculated. A consensus sequence was derived from the first base usage. Similar to studies of SINEs in other species, the analysis showed that most mutations in PREs occur at CpG dinucleotide hot spots. The position variability for the two most frequent bases shows a bimodal distribution. The analysis suggests that the porcine SINEs can be divided into three major subfamilies sharing conserved nucleotide similarities.

Animals↗

PubMed2004

Biocharacteristics shared by highly protective vaccines against Marek's disease.

Attenuated serotype 1 Marek's disease virus strains vary widely in their protection properties. This study was conducted to elucidate which biocharacteristics of serotype 1 MDV strains are related with protection. Three pairs of vaccines, each one including a higher protective (HP) vaccine and a lower protective (LP) vaccine originating from the same MDV strain, were studied. Two other highly protective vaccines (RM1 and CVI988/BP5) were also included in the study. Comparison within pairs of vaccines showed that marked differences existed between the HP and the LP vaccines. Compared with LP vaccines, HP vaccines replicated better in vivo. Also, they induced a significant expansion of total T cells and of the helper and cytotoxic T cell lineages (CD45(+)CD3(+), CD4(+)CD8(-), CD4(-)CD8(+)) as well as a marked increase in the expression of the antigens of MhcI and MhcII on T cells. Thus, our results show that in vivo replication and early stimulation of the T-cell lineage are two characteristics shared by HP vaccines. However, comparison among the four HP vaccines that provided protection equal to that of CVI988 (RM1, CVI988/BP5, CVI988 and 648A80) revealed variability, especially regarding in vivo replication. Strains RM1 and CVI988/BP5 showed much stronger replication in vivo than the other two vaccine strains (CVI988 and 648A80). Thus, no single set of characteristics could be used to identify the most protective Marek's disease vaccines, implying, perhaps, that multiple mechanisms may be involved.

Animals↗

PubMed2026

Mendelian disorders of the epigenetic machinery: a decade of insights into the molecular basis.

The Mendelian disorders of the Epigenetic Machinery (MDEMs), or Chromatinopathies, are now understood to be a collectively common cause of childhood neurodevelopmental delays and intellectual disability. In the past decade, the chromatin and gene expression consequences of heterozygous chromatin regulator disruption have been investigated in various disease models, yielding insights into the molecular pathogenesis of MDEMs. In this review, we highlight some of these results - drawing upon studies of representative MDEMs - together with potential unifying concepts. We propose that MDEMs are characterized by distributed, often subtle chromatin and gene expression perturbations, which impact diverse cellular pathways and processes and are frequently shared between distinct disorders. In this sense, they occupy an intermediate space between classical monogenic disorders and complex traits. We propose potential explanations for the variable expressivity in MDEMs and conclude by considering how technological advances can now enable a deeper and more precise mechanistic characterization of this important Mendelian disease group.

Humans↗