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Biomedical subjects

J L Ross

Publications and source records attributed to J L Ross.

At least 37 records · Page 2Linked to original sources
PubMed1997

Neuroblastoma and related tumors in Turner's syndrome.

OBJECTIVES: The identification of constitutional cytogenetic abnormalities in patients with cancer may indicate loci of genes, abnormalities of which are responsible for tumor development or progression. This study was undertaken to determine whether girls with Turner's syndrome (TS) (partial or complete deletion of an X chromosome, short stature, gonadal dysgenesis) are at increased risk of neural crest-derived tumors. STUDY DESIGN: Medical records of 394 patients with TS who were followed up at Thomas Jefferson Hospital and Children's Hospital of Pittsburgh were reviewed for documentation of TS phenotype, constitutional cytogenetics, and history of neuroblastoma or related tumors. Informative cases were reviewed for tumor pathology, primary site, disease stage, associated symptoms, treatment, and outcome. RESULTS: Three patients were found to have neuroblastoma. A fourth child who died of neurofibrosarcoma was found to have extensive areas of ganglioneuroma, the benign counterpart of neuroblastoma, at autopsy. An additional four girls with TS and neuroblastoma were identified in the literature, as were two more patients with ganglioneuroma. These 10 patients ranged in age from 1 week to 16 10/12 years (median age, 3 years), and all but two of the children had localized lesions. Two of the seven children with neuroblastoma had courses complicated by opsoclonus-myoclonus, a syndrome found in fewer than 5% of all patients with neuroblastoma. CONCLUSIONS: These data strongly suggest that girls with TS are predisposed to the development of neuroblastoma and related tumors. Because these tumors are often of limited stage and may be underdiagnosed, screening of urine of patients with TS for elevated catecholamine metabolite levels may strengthen this association.

Adolescent↗
PubMed1997

Del (X)(p21.2) in a mother and two daughters with variable ovarian function.

We report a family in which a woman with the mosaic karyotype 45,X/46,X,del(X)(p21.2) transmitted the deleted X chromosome to two daughters. The nature of the deletion was confirmed by fluorescent in situ hybridization (FISH). All three family members showed somatic Ullrich-Turner syndrome features, but only one daughter had ovarian failure. These observations have implications for the diagnosis of Ullrich-Turner syndrome and genotype/phenotype correlations of X chromosome deletions.

Abnormalities, Multiple↗
PubMed1997

Absence of growth hormone effects on cognitive function in girls with Turner syndrome.

Turner syndrome (TS) is a genetic disorder characterized by short stature, gonadal dysgenesis, and a particular neurocognitive profile of normally developed language abilities (particularly verbal IQ) and impaired visual-spatial and/or visual-perceptual abilities. We have followed a large sample of girls with Turner syndrome who were enrolled in a long-term, double-blind, placebo-controlled trial of the effects of growth hormone (GH) treatment on final adult height. This study provides a unique opportunity to prospectively evaluate the effects of GH treatment on neurocognitive function in this population of girls with Turner syndrome. The GH- and placebo-treated Turner syndrome subjects were well matched for age, treatment duration, race, karyotype, and socioeconomic status. Treatment (GH or placebo) durations ranged from 1-7 yr. Whether GH deficiency and/or treatment in childhood and adolescence influences cognitive outcome in short children or GH-children is controversial. The major result of this study was the absence of GH treatment effects on cognitive function in girls with Turner syndrome. Our findings are in agreement with most of the previous studies that found no apparent growth hormone treatment effects on cognitive function in growth-hormone deficient children. We conclude that this study does not support a role for growth hormone in influencing childhood brain development in girls with Turner syndrome. Their characteristic nonverbal neurocognitive deficits were not altered with GH treatment into early adolescence.

Child↗
PubMed1997

Adolescent self-esteem and locus of control: a longitudinal study of gender and age differences.

The questions of whether self-esteem and locus of control change during the high school years, and whether gender differences exist in these variables were considered in this study. Participants consisted of 174 students who were ninth graders in 1989 and who were surveyed each spring for four years. Two-way ANOVAs were used to measure changes in self-esteem and locus of control over the four years as well as gender differences. A significant main effect for gender with lower self-esteem scores for girls was found. For locus of control, there was a significant main effect for grade and an interaction between grade and gender.

Adolescent↗
PubMed1996

Developmental changes in motor function in girls with Turner syndrome.

The Turner syndrome phenotype is characterized by a particular neurocognitive profile of normal verbal skills, impaired visuospatial and/or visuoperceptual abilities, and difficulty with motor function. We investigated motor function in non-estrogen-treated girls (ages 7-9 and 10-12 years) with Turner syndrome and age-matched female controls. Our goal was to delineate the differences in motor performance between girls with Turner syndrome (n = 78) and control girls (n = 145). Cognitive and motor tasks were administered, as well as nonspatial, repetitive motor tasks, and spatially mediated motor tasks. Questionnaires were also administered. Turner subjects performed less well than the controls on the motor tasks with the greatest spatial demands, particularly in the older age group (age 10-12.9 years). The older control group, unlike the older Turner syndrome group, had significantly increased speed on most of the motor tasks, suggesting a Turner syndrome-associated deficiency in motoric development. The superior performance of the dominant (right) versus the nondominant (left) hand was similar for the Turner syndrome and control groups. In general, the girls with Turner syndrome had evidence of a decreased sense of athletic ability and physical self-image. A likely explanation for motoric deficiency in the older Turner syndrome group relates to their gonadal dysgenesis and estrogen deficiency. In addition to the obvious physical benefits of estrogen replacement, estrogen treatment may have a positive impact on motor function; this will be the subject of future investigations.

Child↗
PubMed1996

Brain development, gender and IQ in children. A volumetric imaging study.

Normal brain development during childhood is a complex and dynamic process for which detailed scientific information is lacking. MRI techniques, combined with methods for advanced image analysis, offer the potential to begin to construct a quantitative map of normal paediatric brain development in vivo. In this study we utilize volumetric analysis of high resolution brain images obtained from MRI to describe cerebral development and morphology in 85 normal children and adolescents ranging in age from 5 to 17 years. The results show that total cerebral volume is 10% larger in boys compared with girls. However, both boys and girls show little change in total cerebral volume after the age of 5 years. Increased cortical grey matter is the primary contributor to larger brain volume in boys, thus supporting the hypothesis that gender associated differences in brain size are related to differences in cortical neuronal density. Prominent, age-related changes in grey matter, white matter and CSF volumes are evident during childhood and appear to reflect ongoing maturation and remodelling of the CNS. Both boys and girls show a similar pattern of cerebral asymmetry; a rightward prominence of cortical and subcortical grey matter and a leftward prominence of CSF is observed. IQ is positively correlated with total cerebral volume in children, in particular, with the volume of cortical grey matter in the prefrontal region of the brain. Subcortical grey matter also contributes to the variance in IQ, although to a lesser extent than cortical grey volume. Quantitative knowledge of the developing human brain will play an increasingly greater role in improving sensitivity and specificity in the interpretation of brain abnormalities in patients within the clinical environment, as well as in groups of children with suspected brain dysfunction in the research setting.

Adolescent↗
PubMed1996

Self-concept and behavior in adolescent girls with Turner syndrome: potential estrogen effects.

Data on self-concept and behavior were gathered from 31 girls with Turner syndrome (TS) followed longitudinally between the ages of 12 and 16 and from 89 normal control girls recruited from public schools and assessed cross-sectionally. The two groups of girls were similar in age and racial composition. The girls with TS were treated with estrogen replacement therapy in increasing doses between the ages of 12 and 16 (100-400 ng/kg-day ethinyl estradiol). Their self-reported self-esteem and psychological well-being (Piers-Harris Self-Concept Scale) revealed significant improvement over time for most scales as well as the total score (P < 0.001). Parents reported improvement in problem behaviors, as reflected in the Child Behavior Checklist (CBCL) scales: Behavior Total, Externalizing Behavior, Aggressive Behavior, and Social Problems Behavior scales (all P < 0.001). Analysis of covariance comparing normal controls to the TS subjects revealed that at age 12 yr, TS and normal subjects differed significantly for the School Social Competency sub-scale and the Social Problems Behavior subscale (all P < 0.001). Girls with TS resembled the normal controls on all CBCL scales by ages 14-15 yr. Thus, we found improved self-concept both by self- and parental report in estrogen-treated girls with TS followed longitudinally through adolescence. An analogous correlation with age was not seen in the cross-sectional normal control sample. These findings support positive effects of estrogen on psychological well-being in girls with TS and underscores the need to initiate estrogen replacement therapy by ages 12-14 yr in this population.

Adolescent↗
PubMed1995

Activation of IL-2 receptor alpha-chain gene by individual members of the rel oncogene family in association with serum response factor.

Expression of the IL-2R alpha gene is regulated by members of the c-Rel/NF-kappa B family of transcription factors binding to the kappa B site in the promoter. Previous work has not defined the role of individual members of the c-Rel family in the activation of the IL-2R alpha gene. Using the COS cell system, we were able to reconstitute the regulation of the IL-2R alpha promoter by expressing cloned Rel family members with serum response factor (SRF). We found that c-rel alone activated the IL-2R alpha promoter only weakly but worked with the p50 subunit of NF-kappa B (NFKB1) to give a higher level of expression. We showed that c-rel heterodimerizes with p50 and the amount of this heterodimer correlated with the level of IL-2R alpha gene expression. Our results provide evidence that c-rel/p50 heterodimers activate gene expression in the context of a cellular promoter. We show that c-rel or p65 can cooperate with SRF in the activation of this promoter and the transactivation by c-rel with SRF was enhanced by p50. Synergistic activation required both kappa B and CArG sites, and binding studies show that these adjacent sites can be occupied simultaneously. The transactivation observed with cloned transcription factors mimics the physiologic induction of the IL-2R alpha gene since multiple sequence elements cooperate to give gene activation. The data support the model that c-rel/p50 or p65 can cooperate with SRF to specifically target the expression of the IL-2R alpha gene in activated T cells.

Amino Acid Sequence↗
PubMed1995

Ullrich-Turner syndrome: neurodevelopmental changes from childhood through adolescence.

Our objective was to investigate whether the previously-described neurocognitive pattern in girls with Ullrich-Turner syndrome is found in childhood and adolescence; we used a prospective, controlled study of neurocognitive development in girls with Ullrich-Turner syndrome. The patients included 56 girls with Ullrich-Turner syndrome, and 100 normal age- and verbal IQ-matched female control subjects, whose ages ranged from 6-14 years. All girls with Ullrich-Turner syndrome and the normal control girls received a battery of neurocognitive tests designed to evaluate the following domains: general cognition, memory, academic achievement, language, visual-spatial/perceptual skills, visual-motor skills, attention, and affect recognition. Our results demonstrated consistent findings in Ullrich-Turner syndrome girls across the age range studied. In general, the Ullrich-Turner girls resembled control subjects in terms of verbal and language abilities. We found relatively depressed performance IQ and a significant verbal IQ-performance IQ difference. Significant differences were observed on examination of nonverbal abilities. The Ullrich-Turner girls performed more poorly than control girls on 1) tests of visual-motor skills including the Beery Test of Visual-Motor Integration, the Perceptual Organization Factor, and the Rey-Osterrieth Figures; 2) tests of visual-spatial skills, including the Motor-Free Visual Perception Test; 3) tests of attention, including the Freedom From Distractibility Factor; and 4) the Affective Prosody Affect Recognition Test. Ullrich-Turner subjects showed evidence of multifocal or diffuse right cerebral dysfunction and deficits generally involving nonverbal skills that may be due to X chromosome monosomy, gonadal dysgenesis, or both. Future studies will examine the role of estrogen replacement on cognitive function in Ullrich-Turner syndrome individuals.

Adolescent↗
PubMed1995

Neurodevelopmental effects of X monosomy: a volumetric imaging study.

Thirty girls with Turner syndrome (TuS) were compared with 30 individually age-matched controls on volumetric brain measures derived from magnetic resonance imaging and on measures of psychological functioning. As expected, girls with TuS performed more poorly on visual-spatial and intellectual measures relative to controls, and were rated by their parents as having more significant problems in attention and social behaviors. Although no group differences in overall cerebral or subcortical volumes were observed, the regional distribution of gray and white matter differed across groups in both right and left parietal regions. Differences in total tissue volume ratios were seen for both right and left parietal areas, but differences in individual gray and white matter ratios were seen exclusively in the right parietal regions. In general, girls with TuS had a smaller proportion of tissue (gray and white) within the right and left parietal regions, and a larger proportion of tissue within the right inferior parietal-occipital region relative to girls in the control group. These data suggest a potentially important role for X chromosome genes and/or sex steroids in the development and specialization of brain structure and function.

Adolescent↗
PubMed1995

Lipid abnormalities in Turner syndrome.

Turner syndrome is associated with insulin resistance, increased incidence of type II diabetes, and hypertension, all of which are cardiovascular risk factors. The purpose of this study was to evaluate the lipid profile of girls with untreated Turner syndrome, (aged 5 to 14 years; 68% 45,XO) and age-matched, normal girls. A total of 137 girls with Turner syndrome and 70 normal girls had lipid profile measurements, including cholesterol, high-density lipoprotein cholesterol, and triglycerides. Older girls with Turner syndrome (> 11.0 years) had increased cholesterol levels (p < 0.01), compared with control values (190 +/- 38 vs 165 +/- 26 mg/dl). Cholesterol levels were elevated in older subjects with Turner syndrome versus normal subjects, after adjustment for age, karyotype, and body mass index z score effects (p = 0.01). In the subjects with Turner syndrome but not the normal subjects, serum cholesterol values correlated with age, weight, and body mass index z score (p < 0.02). We conclude that adolescent girls with untreated Turner syndrome have significantly increased cholesterol levels, independent of age, body mass index z score, or karyotype, and that these precede any treatment with exogenous estrogen or growth hormone.

Adolescent↗
PubMed1995

Growth hormone hypersecretion in a girl with McCune-Albright syndrome: comparison with controls and response to a dose of long-acting somatostatin analog.

GH every 20 min for 24 h, insulin-like growth factor I (IGF-I), IGF-binding protein 3, and estradiol (E2) were measured in a 7.3-yr-old girl with precocious puberty due to McCune-Albright syndrome (MAS) who developed stigmata of early acromegaly and in 9 other MAS patients who had no signs of acromegaly. To determine whether the MAS patients had subtle abnormalities in GH secretion, a computerized pulse analysis program was used to compare the MAS data with those from 27 control girls with central precocious puberty who had a similar rate of bone age advance, E2, and body mass index. We found no differences in mean GH, GH pulse frequency, pulse height, or pulse area between MAS patients and controls except in patient 1, who had an elevated mean +/- SD GH compared with controls (15.4 +/- 2 vs. 4.8 +/- 2.3 micrograms/L; P < 0.01) and an elevated IGF-I (908 micrograms/L) and IGF-binding protein 3 (5.6 mg/L). None of the GH parameters correlated with body mass index, age, bone age, or E2 levels in either group. The serum GH in patient 1 fell to near-undetectable levels from 60-180 min after a 100-micrograms sc dose of long-acting somatostatin, confirming that this form of therapy can be effective in cases of GH hypersecretion due to MAS.

Child↗
PubMed1995

Self-esteem and behavior in girls with Turner syndrome.

Data on social competence, behavior, and self-esteem were gathered from a large sample of girls with Turner syndrome to determine whether psychological difficulties were associated with Turner syndrome. Subjects included 97 girls with Turner syndrome, 7 to 14 years of age, and 93 girls without Turner syndrome recruited from public schools. The two groups of girls were similar in age, verbal intelligence scores, and racial composition. The girls with Turner syndrome were found, based on both parental and self-report, to be more immature than the girls in the comparison group, with weaker social relationships, school performance, and self-esteem. A decline in self-esteem was also documented for the girls with Turner syndrome, but not the comparison group, as they moved into early adolescence. Although the findings support an increased risk for subtle behavioral problems among girls with Turner syndrome, in most cases the problems endorsed were not severe enough to suggest clinical impairment.

Child↗
PubMed1994

An evolutionarily conserved palindrome in the Drosophila Gld promoter directs tissue-specific expression.

A conserved palindromic sequence (Gpal) in the promoter region of the Drosophila Gld directs expression of a heterologous reporter gene in transgenic flies to the anterior spiracular glands of third instar larvae and to the ejaculatory bulb of adult males. The Gld gene is normally expressed at high levels in the anterior spiracular glands but is not expressed in the ejaculatory bulb of Drosophila melanogaster. However, Gld promoters from other Drosophila species contain the Gpal element and express glucose dehydrogenase (GLD) in the adult male ejaculatory bulb. A gene fusion composed of the D. melanogaster Gld promoter and the lacZ gene is expressed in the anterior spiracular glands of transgenic larvae. Mutations of the Gpal sequence element in this gene fusion block expression of beta-galactosidase in the anterior spiracular gland. Together these experiments demonstrate that Gpal is necessary and sufficient for tissue-specific expression in the anterior spiracular glands. Based upon the tissue distribution and function of GLD, it is speculated that expression of GLD in the anterior spiracular glands represents the ancestral state and that GLD expression in other tissues arose as a fortuitous consequence of a shared combinatorial regulatory network.

Animals↗
PubMed1994

A model of the Drosophila melanogaster glycerol-3-phosphate oxidase-encoding gene.

We have sequenced the Drosophila melanogaster gene encoding the mitochondrial (mt) enzyme glycerol-3-phosphate oxidase (GPO; EC 1.1.99.5) that is involved in flight and alcohol metabolism. Available data suggests a simple model for this gene that includes four exons. Exon I contains a mt import signal, exon II, a transmembrane segment and an FAD-binding site, and exon IV, an iron-sulfur centre.

Alternative Splicing↗
PubMed1994

Correlated evolution of the cis-acting regulatory elements and developmental expression of the Drosophila Gld gene in seven species from the subgroup melanogaster.

The tissue-specific expression patterns of glucose dehydrogenase (GLD) exhibit a high degree of interspecific variation in the adult reproductive tract among the species in the genus Drosophila. We chose to focus on the evolution of GLD expression and the evolution of the Gld promoter in seven closely related species in the melanogaster subgroup as a means of elucidating the relationship of changes in cis-acting regulatory elements in the Gld promoter region with changes in tissue-specific expression. Although little variation in tissue-specific patterns of GLD was found in nonreproductive tissues during development, a surprisingly high level of variation was observed in the expression of GLD in both developing and mature reproductive organs. In some cases this variation is correlated with changes in sequence elements in the Gld promoter which were previously shown to direct tissue-specific expression in the reproductive tract. In particular D. teissieri adult males do not express GLD in their ejaculatory ducts, atypical of the melanogaster subgroup species. The Gld promoter region of D. teissieri specifically lacks all three of the TTAGA regulatory elements present in D. melanogaster. The TTAGA elements were previously shown to direct reporter gene expression to the ejaculatory duct. Together these data suggest the absence or presence of the TTAGA elements may be responsible for variation in the absence or presence of GLD in the ejaculatory duct among species.

Animals↗
PubMed1994

EVA design: lessons learned.

Extravehicular Activities (EVAs) are very demanding and specialized space flight activities. There are many aspects to consider in the design of hardware, tools, and procedures to be used on an EVA mission. To help minimize costs and optimize the EVA productivity, experience shows that astronauts should become involved early in the design process.

Astronauts↗