Biomedical subjects

J L Ross

Publications and source records attributed to J L Ross.

At least 19 recordsLinked to original sources

PubMed2002

Persistent cognitive deficits in adult women with Turner syndrome.

BACKGROUND: Turner syndrome (TS) has a characteristic neurocognitive profile. Verbal abilities are, in general, normal; however, women with TS, as a group, have specific deficits in visual-spatial abilities, visual-perceptual abilities, motor function, nonverbal memory, executive function, and attentional abilities. Observed deficits could be caused by genetic or endocrine factors. OBJECTIVE: To evaluate the specific cognitive deficits that appear to persist in adulthood, are not estrogen-responsive, and may be genetically determined. METHODS: The cognitive performance of adult women with TS (n = 71) who were estrogen repleted was compared with verbal IQ- and socioeconomic status-matched female controls (n = 50). Sixty-one women with TS had ovarian failure and received estrogen replacement and 10 had preserved endogenous ovarian function and were not receiving estrogen replacement at the time of evaluation. RESULTS: Similar to children and adolescents with TS, adults with TS have normal verbal IQ but have relative difficulty on measures of spatial/perceptual skills, visual-motor integration, affect recognition, visual memory, attention, and executive function despite estrogen replacement. These deficits are apparent in women with TS despite apparently adequate estrogen effect, either endogenous or by hormone replacement. CONCLUSION: The cognitive phenotypes of adults with TS, with or without ovarian failure, are similar, indicating that estrogen replacement does not have a major impact on the cognitive deficits of adults with TS.

Adolescent↗

PubMed2001

A man who inherited his SRY gene and Leri-Weill dyschondrosteosis from his mother and neurofibromatosis type 1 from his father.

We report on a man with neurofibromatosis type 1 (NF1) and Leri-Weill dyschondrosteosis (LWD). His father had NF1. His mother had LWD plus additional findings of Turner syndrome (TS): high arched palate, bicuspid aortic valve, aortic stenosis, and premature ovarian failure. The proband's karyotype was 46,X,dic(X;Y)(p22.3;p11.32). Despite having almost the same genetic constitution as 47,XXY Klinefelter syndrome, he was normally virilized, although slight elevation of serum gonadotropins indicated gonadal dysfunction. His mother's karyotype was mosaic 45,X[17 cells]/46,X,dic(X;Y)(p22.3;p11.32)[3 cells].ish dic(X;Y)(DXZ1 +,DYZ1 + ). The dic(X;Y) chromosome was also positive for Y markers PABY, SRY, and DYZ5, but negative for SHOX. The dic(X;Y) chromosome was also positive for X markers DXZ1 and a sequence < 300 kb from PABX, suggesting that the deletion encompassed only pseudoautosomal sequences. Replication studies indicated that the normal X and the dic(X;Y) were randomly inactivated in the proband's lymphocytes. LWD in the proband and his mother was explained by SHOX haploinsufficiency. The mother's female phenotype was most likely due to 45,X mosaicism. This family segregating Mendelian and chromosomal disorders illustrates extreme sex chromosome variation compatible with normal male and female sexual differentiation. The case also highlights the importance of karyotyping for differentiating LWD and TS, especially in patients with findings such as premature ovarian failure or aortic abnormalities not associated with isolated SHOX haploinsufficiency.

Adult↗

PubMed2001

Safety and effectiveness of Niaspan when added sequentially to a statin for treatment of dyslipidemia.

Niaspan, when added to a stable dose of a statin in 66 subjects, was found to be safe and highly effective in improving lipid parameters. Subgroup analyses demonstrated its effectiveness in lowering low-density lipoprotein cholesterol in persons not at the National Cholesterol and Education Program low-density lipoprotein cholesterol target and in raising high-density lipoprotein cholesterol in persons with levels < 40 mg/dl.

Adult↗

PubMed2001

Molecular analysis of genes on Xp controlling Turner syndrome and premature ovarian failure (POF).

Monosomy X has been known to be the chromosomal basis of Turner syndrome (TS) for more than four decades. A large body of cytogenetic data indicates that most TS features are due to reduced dosage of genes on the short arm of the X chromosome (Xp). Phenotype mapping studies using molecular cytogenetic and genetic techniques are beginning to localize the Xp genes that are important for various TS features, and a comprehensive catalog of candidate genes is becoming available through the Human Genome Project and related research. It is now possible to assess the contributions of individual genes to the TS phenotype by mutational analysis of karyotypically normal persons with specific TS features. This strategy has succeeded in identifying a gene involved in short stature and is being applied to premature ovarian failure and other TS phenotypes.

Body Height↗

PubMed2001

Psychosocial development in adolescents with Turner syndrome.

Turner syndrome is a genetic condition in which part or all of the second X chromosome is missing. Our goal in this study was to examine the psychosocial adjustment of a sample of adolescent girls with Turner syndrome. Subjects included 122 girls with a diagnosis of Turner syndrome (TS) and a control group of 108 girls with no genetic disorder or chronic illness. Subjects were 13 to 18 years of age. A battery of questionnaires assessing social, academic, school, and behavioral functioning was administered. TS girls were seen as having significantly more problems in terms of social relationships and school progress and were more likely to meet criteria for attention-deficit hyperactivity disorder than control girls. The TS girls were also rated by a parent as less socially competent (e.g., fewer friends, less time with friends) than the control group. Social difficulties appear to be an area of vulnerability for TS girls. Counseling individuals with Turner syndrome and their families about the need to carefully develop and nurture social skills and relationships may prove useful in advancing the social adaptation of these young women.

Adaptation, Psychological↗

PubMed2001

Phenotypes Associated with SHOX Deficiency.

Leri-Weill dyschondrosteosis (LWD) (MIM 127300) is a dominantly inherited skeletal dysplasia characterized phenotypically by Madelung wrist deformity, mesomelia, and short stature. LWD can now be defined genetically by haploinsufficiency of the SHOX (short stature homeobox-containing) gene. We have studied 21 LWD families (43 affected LWD subjects, including 32 females and 11 males, ages 3-56 yr) with confirmed SHOX abnormalities. We investigated the relationship between SHOX mutations, height deficit, and Madelung deformity to determine the contribution of SHOX haploinsufficiency to the LWD and Turner syndrome (TS) phenotypes. Also, we examined the effects of age, gender, and female puberty (estrogen) on the LWD phenotype. SHOX deletions were present in affected individuals from 17 families (81%), and point mutations were detected in 4 families (19%). In the LWD subjects, height deficits ranged from -4.6 to +0.6 SD (mean +/- SD = -2.2 +/- 1.0). There were no statistically significant effects of age, gender, pubertal status, or parental origin of SHOX mutations on height z-score. The height deficit in LWD is approximately two thirds that of TS. Madelung deformity was present in 74% of LWD children and adults and was more frequent and severe in females than males. The prevalence of the Madelung deformity was higher in the LWD vs. a TS population. The prevalence of increased carrying angle, high arched palate, and scoliosis was similar in the two populations. In conclusion, SHOX deletions or mutations accounted for all of our LWD cases. SHOX haploinsufficiency accounts for most, but not all, of the TS height deficit. The LWD phenotype shows some gender- and age-related differences.

Adolescent↗

PubMed2000

The Turner syndrome-associated neurocognitive phenotype maps to distal Xp.

Turner syndrome (TS) is associated with a characteristic neurocognitive profile that includes impaired visuospatial/perceptual abilities. We used a molecular approach to identify a critical region of the X chromosome for neurocognitive aspects of TS. Partial deletions of Xp in 34 females were mapped by FISH or by loss of heterozygosity of polymorphic markers. Discriminant function analysis optimally identified the TS-associated neurocognitive phenotype. Only subjects missing approximately 10 Mb of distal Xp manifested the specified neurocognitive profile. The phenotype was seen with either paternally or maternally inherited deletions and with either complete or incomplete skewing of X inactivation. Fine mapping of informative deletions implicated a critical region of <2 Mb within the pseudoautosomal region (PAR1). We conclude that haploinsufficiency of PAR1 gene(s) is the basis for susceptibility to the TS neurocognitive phenotype.

Adolescent↗

PubMed2000

Use of estrogen in young girls with Turner syndrome: effects on memory.

BACKGROUND: The Turner syndrome (TS) phenotype is characterized by a specific neurocognitive profile of normal verbal skills, impaired visual-spatial and visual-perceptual abilities, and impaired nonverbal more than verbal memory. We compared verbal and nonverbal memory in estrogen- and placebo-treated girls with TS (ages 7 to 9 years) and age-matched female controls. METHODS: Children received either estrogen (ethinyl estradiol, 25 ng/kg/d) or placebo for 1 to 3 years (mean, 2.1+/-0.9 years) in a randomized, double-blind study. Memory and language tasks administered included the Wechsler Intelligence Scale for Children-Revised, Digit Span (forward and backward), the Children's Word List, the Denman Paragraph, the Peabody Picture Vocabulary Test, Boston Naming, immediate and delayed Recall of the Rey Complex Figure, Nonword Reading, Wide Range Achievement Test-Revised reading subtest, Verbal fluency, and the Token Test. RESULTS: The estrogen-treated TS group performed better than the placebo-treated TS group for the Children's Word List immediate and delayed recall and the Digit Span backwards test (p<0.01 to 0.04), although the results were not significant after adjusting for multiple comparisons. The placebo-treated TS group performed less well than the controls for recall of Digit Span backward (p<0.0001; placebo-treated, 2.8+/-1.3; estrogen-treated, 3.4+/-1.2; and controls, 4.2+/-1.3) and immediate and delayed recall of the Children's Word List (delayed recall, p<0.0001; placebo-treated, 6.2+/-3.1; estrogen-treated, 8.0+/-2.9; and controls, 9.0+/-2.9). Performance for these measures was similar for the estrogen-treated TS group and the control group. CONCLUSIONS: Estrogen replacement therapy in young girls with Turner Syndrome is associated with improved verbal and nonverbal memory. The optimal patient age, dose, and duration of estrogen replacement require further study.

Child↗

PubMed2000

Physical mapping of nine Xq translocation breakpoints and identification of XPNPEP2 as a premature ovarian failure candidate gene.

Women with balanced translocations between the long arm of the X chromosome (Xq) and an autosome frequently suffer premature ovarian failure (POF). Two "critical regions" for POF which extend from Xq13-->q22 and from Xq22-->q26 have been identified using cytogenetics. To gain insight into the mechanism(s) responsible for ovarian failure in women with X;autosome translocations, we have molecularly characterized the translocation breakpoints of nine X chromosomes. We mapped the breakpoints using somatic cell hybrids retaining the derivative autosome and densely spaced markers from the X-chromosome physical map. One of the POF-associated breakpoints in a critical region (Xq25) mapped to a sequenced PAC clone. The translocation disrupts XPNPEP2, which encodes an Xaa-Pro aminopeptidase that hydrolyzes N-terminal Xaa-Pro bonds. XPNPEP2 mRNA was detected in fibroblasts that carry the translocation, suggesting that this gene at least partially escapes X inactivation. Although the physiologic substrates for the enzyme are not known, XPNPEP2 is a candidate gene for POF. Our breakpoint mapping data will help to identify additional candidate POF genes and to delineate the Xq POF critical region(s).

Amino Acid Sequence↗

PubMed2000

Localization of MYOC transcripts in human eye and optic nerve by in situ hybridization.

PURPOSE: To evaluate MYOC (myocilin) gene expression at the RNA level in normal intact human eyes and optic nerve using in situ hybridization. METHODS: Normal human eyes and optic nerves from donors 62 to 83 years of age with no history of glaucoma were fixed, embedded in paraffin, and sectioned. Sections were hybridized with (35)S-labeled sense and antisense riboprobes derived from a full-length MYOC cDNA. RESULTS: High levels of MYOC expression were observed throughout the trabecular meshwork as well as in the most anterior nonfiltering meshwork (Schwalbe's line), in the scleral spur, and in the endothelial lining of Schlemm's canal. MYOC transcripts were also detected in the anterior corneal stroma, in the ciliary muscle, beneath the anterior border of the iris, in the iris stroma, and in the sclera. Expression in the retrolaminar region of the optic nerve was present in the pial septa that divide the nerve fiber bundles, in the perivascular connective tissue surrounding the central retinal vessels, and in the dura mater, arachnoid, and pia mater of the meningeal sheath surrounding the optic nerve. CONCLUSIONS: MYOC gene expression in the trabecular meshwork, Schlemm's canal, scleral spur, and ciliary muscle indicates a structural or functional role for myocilin in the regulation of aqueous humor outflow that may influence intraocular pressure. MYOC expression in the optic nerve suggests that changes in the structural, metabolic, or neurotropic support of the optic nerve may influence its susceptibility to glaucomatous damage.

Aged↗

PubMed1999

An innovative approach to temporary hemodialysis vascular access.

The National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) has set down explicit and extensive guidelines for temporary and permanent hemodialysis vascular access. It is now incumbent on the nephrologist to ensure compliance to these standards. Two of our interventional nephrologists performed 402 central venous access procedures over a 12-month period (November 1996 to October 1997) to test the hypothesis that increased control over insertion technique would improve outcome. All but eight of the procedures were successfully completed, resulting in a failure rate of 2%. The expected serious procedural complication rate outlined in the NKF-DOQI standards is 2%. Our complication rate was 0.7% if all procedures were accounted for and 0.89% for just internal jugular and subclavian catheters. We conclude that the use of interventionally trained nephrologists and strict control of technique can improve outcome in temporary vascular access procedures.

Arteriovenous Shunt, Surgical↗

PubMed1998

Transition to young adulthood in Ullrich-Turner syndrome: neurodevelopmental changes.

Studies describing the neurocognitive profile of Ullrich-Turner syndrome (UTS) have focused primarily on neurodevelopmental changes in childhood and adolescence or in adults with UTS. The objective of the present study was to describe neurodevelopmental changes that occur in UTS females during the transition from adolescence to young-adulthood. The subjects included 99 females with UTS and 89 normal female controls matched for age and socioeconomic status. Subjects were between the ages of 13 and 21 years. All subjects received a battery of neurocognitive tests designed to assess general cognitive ability, academic achievement, memory, language, executive function, visual-spatial/perceptual and motor skills, affect recognition, attention, and motor skills. Results from our study indicated that females with UTS performed significantly less well than controls on measures of spatial/perceptual skills, visual-motor integration, affect recognition, visual memory, attentional abilities, and executive function, consistent with previous reports of cognitive abilities in adolescent UTS females. Moreover, our results indicate that decreased performance in some of these areas persists through late adolescence and into early adulthood while improvement occurs in other areas. It is possible that catch-up in certain cognitive deficiencies in UTS females represents a maturational/developmental lag. Alternatively, the neurodevelopmental changes that were observed in UTS females may result from the cumulative effects of estrogen replacement therapy during adolescence. Therapeutic interventions specific to the demands of young-adulthood are also discussed.

Adolescent↗

PubMed1998

Turner syndrome and haploinsufficiency.

Turner syndrome was one of the first human genetic disorders ascribed to haploinsufficiency but the identification of specific genes responsible for the phenotype has been problematic. Recent data point to several candidate genes, some new and some old, for specific aspects of the phenotype associated with monosomy X in humans.

Animals↗

PubMed1998

Evidence for a Turner syndrome locus or loci at Xp11.2-p22.1.

Turner syndrome is the complex human phenotype associated with complete or partial monosomy X. Principle features of Turner syndrome include short stature, ovarian failure, and a variety of other anatomic and physiological abnormalities, such as webbed neck, lymphedema, cardiovascular and renal anomalies, hypertension, and autoimmune thyroid disease. We studied 28 apparently nonmosaic subjects with partial deletions of Xp, in order to map loci responsible for various components of the Turner syndrome phenotype. Subjects were carefully evaluated for the presence or absence of Turner syndrome features, and their deletions were mapped by FISH with a panel of Xp markers. Using a statistical method to examine genotype/phenotype correlations, we mapped one or more Turner syndrome traits to a critical region in Xp11.2-p22.1. These traits included short stature, ovarian failure, high-arched palate, and autoimmune thyroid disease. The results are useful for genetic counseling of individuals with partial monosomy X. Study of additional subjects should refine the localization of Turner syndrome loci and provide a rational basis for exploration of candidate genes.

Adolescent↗

PubMed1998

Effects of estrogen on nonverbal processing speed and motor function in girls with Turner's syndrome.

The Turner syndrome (TS) phenotype is characterized by a specific neurocognitive profile of normal verbal skills, impaired visual-spatial and/or visual-perceptual abilities, and difficulty with motor function. In the current study, we investigated motor function and nonverbal processing speed in estrogen- and placebo-treated girls (aged 10-12 years) with TS and in age-matched female controls. The goal of this study was to examine whether estrogen replacement therapy would reverse deficits in motor function and in nonverbal processing speed, a measure of the time required to perform certain disparate nonverbal tasks, in adolescent girls with TS. Children received either estrogen (ethinyl estradiol, 12.5-50 ng/kg.day), or placebo for durations of 1-7 yr (mean, 4.0 +/- 2.1 yr) in this randomized, double blind study. Cognitive and motor tasks administered included the Wechsler Intelligence Scale for Children-Revised; nonspatial, repetitive motor tasks (tapping and three tasks from the Paness); and spatially mediated motor tasks [nongrooved pegboard (Lafayette), pursuit rotor, visual-motor integration, and money street map]. Questionnaires administered included the Self-Concept Scale. The major result of this study was the positive estrogen treatment effect on nonverbal processing speed and speeded motor performance in 12-yr-old TS girls. That motor performance would be slower in estrogen-deficient TS females is consistent with previous studies of the influence of estrogen on motor function. Estrogen replacement is thus the most likely explanation for the improved motor speed and nonverbal processing time in the estrogen-treated TS girls compared to that in the placebo-treated TS girls. Whether these findings will influence the psychoeducational outcome or quality of life of females with TS is not yet known.

Child↗

PubMed1997

Discriminant analysis of the Ullrich-Turner syndrome neurocognitive profile.

Ullrich-Turner syndrome (UTS), or monosomy X, 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. The most frequently described profile in UTS includes difficulty with tasks involving memory and attention, decreased arithmetic skills, and impaired visual spatial processing. We used discriminant function analysis (DFA) to distinguish between the neurocognitive profiles of girls with UTS vs. controls matched for age, height, IQ, and socioeconomic status. DFA is a statistical method for deriving a linear function that optimally weights parameters to permit sensitive and specific differentiation among groups. We developed a modified discriminant function, based on seven cognitive test scores, that successfully discriminated between the UTS and control subjects with a sensitivity of 0.45 and a specificity of 0.97. To validate its performance, we applied the discriminant function to a small group of 45,X UTS subjects (n = 13) and control female subjects (n = 25), ages 7-16 years, who were not part of the previous analyses. The discriminant function (DF) identified 54% of these 13 UTS subjects as having the "UTS neurocognitive profile" and 92% of the 25 control subjects as not having the profile. We also compared the DF scores of UTS girls with various mosaic karyotypes and found that the group with 46,XX mosaicism had significantly higher scores (i.e., closer to normal controls) than the other two mosaic groups (t = 2.86, P < 0.005). The results of this study should be useful for genetic counseling and planning educational programs for girls with UTS.

Adolescent↗

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↗