Biomedical subjects

D Babcock

Publications and source records attributed to D Babcock.

At least 19 recordsLinked to original sources

PubMed2002

Prenatal ultrasound findings in a fetus with congenital contractural arachnodactyly.

Congenital contractural arachnodactyly (CCA) or Beals-Hecht syndrome is an autosomal dominant disorder caused by mutations in the fibrillin-2 (FBN2) gene. The principal features of CCA are a marfanoid habitus, multiple congenital contractures, camptodactyly, arachnodactyly, kyphoscoliosis, muscular hypoplasia, and external ear malformations. Our case is the first that shows typical sonographic signs in a fetus at 25 weeks' gestation with molecular genetically verified CCA in a large family with many members affected over four generations. This demonstrates that CCA can be detected prenatally by non-invasive ultrasonography. The importance of confirmation of CCA by means of DNA sequence analysis of the FBN2 gene is stressed.

Adult↗

PubMed1998

A single mutation that results in an Asp to His substitution and partial exon skipping in a family with congenital contractural arachnodactyly.

Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder of connective tissue and is characterized by multiple congenital contractures, arachnodactyly, and external ear malformations. Recent investigations indicate that mutations in the fibrillin-2 gene (FBN2) cause CCA. Here, we report a G-->C transversion at nucleotide 3340 (G3340C) of FBN2 in a family with phenotypic characteristics of CCA. The G3340C mutation predicts the substitution of histidine for aspartic acid at amino acid residue 1114 (Asp1114His) and also alters the 5' donor splice site consensus sequence of exon 25. Reverse transcription/polymerase chain reaction and DNA sequence analyses demonstrate that this missense mutation also causes low level in-frame mis-splicing of exon 25 (del exon 25). Consequently, this single point mutation produces a heterogeneous population of mutant fibrillin-2 molecules in a single individual. Despite the complex manifestation of the mutation, it is associated with a relatively mild phenotype. Analysis of FBN2 allele expression in cultured dermal fibroblasts derived from the proband has shown that the mutant allele is preferentially expressed, contributing about 84% of the total transcript. This indicates that an overabundance of mutant transcript does not necessarily correlate with a more severe CCA phenotype.

Aged↗

PubMed1997

A rare branch-point mutation is associated with missplicing of fibrillin-2 in a large family with congenital contractural arachnodactyly.

Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder that is phenotypically similar to but genetically distinct from Marfan syndrome. Genetic-linkage analysis has implicated the fibrillin-2 gene (FBN2) as the CCA locus. Mutation analysis of two isolated CCA patients revealed missense mutations, indicating that defects in FBN2 may be responsible for this disorder. However, cosegregation of a mutant allele with the disease phenotype has not yet been established. We have investigated the primary cause of CCA in a large well-characterized kindred with five generations comprising 18 affected individuals. Previous studies demonstrated linkage of this family's CCA phenotype to FBN2. Mutation analysis of cDNA derived from the proband and her affected brother, using a nonisotopic RNase cleavage assay, revealed the partial skipping of exon 31. Approximately 25% mutant transcript is produced, which is apparently sufficient to cause a CCA phenotype. Sequence analysis of genomic DNA revealed an unusual base composition for intron 30 and identified the mutation, a g-26t transversion, in the vicinity of the splicing branch-point site in intron 30. Genomic DNA from 30 additional family members, both affected and unaffected, then was analyzed for the mutation. The results clearly demonstrate cosegregation of the branch-point mutation with the CCA phenotype. This is the first report of a CCA mutation in a multiplex family, unequivocally establishing that mutation in FBN2 are responsible for the CCA phenotype. In addition, branch-point mutations only very rarely have been associated with human disease, suggesting that the unusual composition of this intron influences splicing stability.

Adult↗

PubMed1996

The locomotor effects of a putative dopamine D3 receptor agonist in developing rats.

Dopamine receptors have been categorized into subfamilies D1 and D2, each with separate roles in dopamine-mediated behaviors. Of the D2 subfamily, the dopamine D3 receptor has been cloned, but the behavioral effects of selectively stimulating the D3 receptor are largely unknown. The purpose of this study was to quantify the locomotor responses of developing rats to the putative dopamine D3 receptor agonist, 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT). One of three doses of 7-OH-DPAT (0.01, 0.10, 1.00 mg/kg) or saline was injected subcutaneously into rats at the age of 10,20,30, or 60 days. Five minutes after the injection, rats were placed in automated activity monitors which recorded locomotor behavior at 5 min intervals for 2 h. The high dose of 7-OH-DPAT increased locomotor activity in rats of all ages. The medium and low doses increased activity in 10- and 20-day-old rats but not in 30- or 60-day-old rats. The level of drug-induced activation peaked at 20 days of age. In 30- and 60-day-old rats, but not 10- and 20-day-old rats, a period of locomotor suppression preceded the activation in response to the high dose of 7-OH-DPAT. In rats aged 20 days and older, the middle and low doses decreased locomotion early in the test session, but activation did not ensue. This dose-response pattern across ontogeny closely resembles that induced by quinpirole, an agonist at the dopamine D2 receptor subfamily.

Age Factors↗

PubMed1996

Reversal of beta-amyloid-induced retention deficit after exposure to training and state cues.

We explored amnesia induced by posttraining injection of beta-amyloid protein (beta A4) in four experiments. Previous reports showed that beta A4 impaired retention of learning maintained either by food reward or by shock relief. The experiments in this paper attempted to determine (1) if the amnesia is specific to the 1-40 beta A4 amino-acid sequence; and (2) if the amnesia can be attributed to a consolidation process. Subjects were 190 male Sprague-Dawley rats, 3 to 6 months old. Subjects were given five training trials on a left-right discrimination in a Y-maze with a food reward and injected immediately afterward with beta A4(1-40) or vehicle. One week later they were trained to criterion. Experiment 1 used a control group that was injected with the reverse-sequence peptide (40-1). The performance of the beta A4(40-1) group was unimpaired. Experiments 2 and 3 attempted to reverse the amnestic effects of beta A4 using noncontingent presentation of aspects of the training context during the retention interval. Experimental subjects in Experiment 2 were exposed to the Y-maze in the absence of reinforcers, 24, 22, and 2 h before retention testing. In Experiment 3, subjects were given a 1-min exposure to the reinforcers, outside the Y-maze, 24 h before retention testing. Both manipulations reversed beta A4-induced amnesia. In Experiment 4, beta A4-induced impairments were reversed by reinjecting beta A4 immediately before retention testing. Results indicate that beta A4 injected after partial training does not interfere with a consolidation process.

Amnesia↗

PubMed1995

Occurrence of a mutation associated with Wolman disease in a family with cholesteryl ester storage disease.

Cholesteryl ester storage disease (CESD) and Wolman disease (McKusick 278000) are two distinct autosomal recessive disorders, both attributable to a severe reduction in acid cholesteryl ester hydrolase/lysosomal acid lipase activity (EC 3.1.1.13). We have identified compound heterozygous mutations in a family with two siblings affected with CESD. Molecular genetic analysis revealed two mutations one of which has previously been seen only in Wolman disease. Analysis of these mutations acting in concert provides new insight into the correlation of genotype with phenotype in these allelic disorders.

Base Sequence↗

PubMed1992

The predictive value of head ultrasound in the ECMO candidate.

Cranial ultrasound (US) examination is the screening technique of choice for assessing preexisting neurological damage in potential neonatal extracorporeal membrane oxygenation (ECMO) candidates. Currently, US evidence of intracranial hemorrhage greater than grade I in severity is a contraindication to ECMO at this ECMO center. In the current study, radiological findings were reviewed in 129 consecutive neonatal ECMO cases in an attempt to identify which pre-ECMO US findings were associated with the development of subsequent intracranial complications while on ECMO. Pre-ECMO head US, post-ECMO head US, and head computed tomography (CT) scans were reviewed retrospectively by one radiology team. Ventricular, parenchymal, and extraaxial fluid abnormalities were recorded for each case. Pre-ECMO US findings were then correlated with the subsequent development of significant intracranial radiological abnormalities noted on post-ECMO studies as well as with clinical data regarding ECMO course and outcome. Results showed that infants with evidence of severe edema or periventricular leukomalacia on pre-ECMO imaging had a 63% incidence of subsequent major intracranial complications. This represents a significantly higher risk than in candidates with a normal examination or evidence of grade I intracranial hemorrhage, subependymal cysts, or mild edema. These results suggest that infants with sonographic evidence of ischemic or anoxic damage on pre-ECMO US are at high risk for the development of significant intracranial complications if ECMO therapy is instituted.

Brain↗

PubMed1991

T-cell receptor variable beta genes show differential expression in CD4 and CD8 T cells.

Studies in transgenic and inbred strains of mice have shown that the critical molecular interactions controlling positive selection involve major histocompatibility complex (MHC), T-cell receptor (TCR), and CD4 or CD8 coreceptor molecules. Correlations have been established between MHC gene products and the percentage of CD4 or CD8 T cells that express specific variable (V) beta-gene products as part of the alpha beta heterodimer. These studies have important implications regarding potential mechanisms of HLA-linked autoimmune diseases in humans. If similar interactions are required for positive selection in humans, one would predict that the TCR repertoire expressed by mature, peripheral blood CD4 and CD8 T cells would vary. To test this hypothesis the expression of specific TCR V beta-region genes by CD4 and CD8 T cells from healthy individuals was compared using both triple-color flow cytometry and polymerase chain reaction based experimental approaches. The results show that the TCR repertoire does vary as a function of CD4 and CD8 T-cell subsets. Among unrelated individuals certain V beta genes were consistently overrepresented in the CD4 population (V beta-5.1, -6.7a, and -18); some were skewed to the CD8 population (V beta-14) while others showed variable patterns (V beta-12 and -17). Deletion of entire V beta gene families was not observed suggesting that this is a rare event in humans. Attempts to correlate the expressed TCR repertoire in humans with HLA alleles will require consideration of these differences in expression as a function of subset.

Antibodies, Monoclonal↗

PubMed1991

The Department of Veterans Affairs Optical Patient Card Workstation.

The Department of Veterans Affairs has developed an optical patient card application which will undergo alpha testing in 1991. The optical cards are carried by patients and contain administrative, clinical, and image information. An optical patient card workstation (OPCW) will read/write these cards and pass this information to the VA Decentralized Hospital Computer Program (DHCP), the VA's health care information system. The intent of this work is to study the potential benefits of this technology to the VA's distributed health care network, with a large mobile patient population. It is hoped that the use of optical cards and the OPCW will enhance clinicians ability to work with a timely composite health record, and expedite the administrative workload of the medical center.

Computer Communication Networks↗

PubMed1989

Neurologic status and intracranial hemorrhage in very-low-birth-weight preterm infants. Outcome at 1 year and 5 years.

Twenty-six very-low-birth-weight preterm infants with and without intracranial hemorrhage (ICH) were followed up prospectively from birth to school age to determine the relationship between ICH and subsequent neurologic and cognitive outcomes. All children had sequential cranial ultrasound examinations at birth and neurologic assessments at 3-month intervals during the first year, at 1 year of age, and at 5 to 6 years; psychometric assessments were done at 5 to 6 years. Seventeen children had no ICH, 3 had grade 1 ICH, 1 had grade 3 ICH, and 5 had grade 4 ICH. The 1-year Amiel-Tison neurologic assessment in 25 infants demonstrated that 14 were normal, 3 were suspect, and 8 were abnormal. By 5 to 6 years of age, 5 of 8 children neurologically abnormal at 1 year remained abnormal, 2 of 3 children neurologically suspect at 1 year remained suspect; while 9 of 15 children neurologically normal at 1 year remained normal, the remaining 6 had become suspect. The predominant neurologic abnormality at 5 to 6 years was subtle neurologic dysfunctioning. The Wechsler Preschool and Primary Scale of Intelligence at 5 to 6 years revealed a mean group IQ score of 92.1. The Beery Visual Motor Integration Test results demonstrated that 18 of 26 children had mild to severe visual motor perceptual difficulties. Severe ICH (grades 3 and 4) correlated with abnormal neurologic performances at 1 and 5 to 6 years. Mild ICH (grade 1) and no ICH did not correlate with any one of the 1-year neurologic classifications. The 1-year status correlated with the 5- to 6-year neurologic outcome best for children who were either neurologically suspect or abnormal at age 1 year. The 1-year neurologic score did not correlate with 5- to 6-year IQ and Beery Visual Motor Integration Test scores.

Cerebral Hemorrhage↗

PubMed1989

Minimal vitamin D and high calcium and phosphorus needs of preterm infants receiving parenteral nutrition.

Preterm infants (birth weight, 1,089 +/- 91 g; gestational age, 28.9 +/- 0.7 weeks; mean +/- SEM) with mixed medical and surgical indications for parenteral nutrition (PN) were observed to determine the adequacy of infusates with fixed, low-dose vitamin D (25 IU/dl) and two combinations of calcium and phosphorus. The duration of low-dose vitamin D PN ranged from 5 to 52 days, with a median of 27 days. Twelve infants were randomly assigned to low (standard) Ca and P doses (5 mM each; 20 mg/dl of Ca and 15.5 mg/dl of P) and 13 high Ca and P doses (15 mM each; 60 mg/dl of Ca and 46.5 mg/dl of P). The maximum daily vitamin D intake was similar for both groups (31 +/- 1.3 versus 33 +/- 1.2 IU/kg). Vitamin D status in either group, as indicated by serum 25-hydroxyvitamin D (25-OHD) concentrations, was normal. There was no significant difference in observed changes of serial measurements of serum calcium, magnesium, phosphorus, alkaline phosphatase, creatinine (Cr), 25-OHD, and vitamin D-binding protein concentrations or urinary Ca:Cr and Mg:Cr ratios. In the low-dose Ca and P group, the serum P level was consistently less than 4 mg/dl in five infants, serum 1,25-dihydroxyvitamin D concentrations were higher, and tubular reabsorption of phosphorus was consistently greater than 95% and significantly higher than in the high-dose Ca and P groups. Severe bone demineralization apparent on X-ray occurred in two infants, with a fractured distal left ulna in one of the two infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium, Dietary↗

PubMed1989

Very-low-birth-weight, preterm infants with or without intracranial hemorrhage. Neurologic, cognitive and cranial MRI correlations at 4-8-year follow-up.

Fourteen very-low-birth-weight (VLBW) preterm infants with and without intracranial hemorrhage (ICH) were prospectively followed from birth to 4 to 8 years for the purpose of determining neurologic and cognitive sequelae associated with ICH severity and to correlate outcomes with brain morphology as determined by Magnetic Resonance Imaging (MRI). Intracranial hemorrhage was documented by cranial ultrasonography performed in early life. Follow-up assessments included neurologic and psychometric examinations and cranial MRI scans. Of six children with no ICH, five had normal results on all three follow-up measures. Three children with Grade I-II ICH had mild to moderate neurologic and cognitive sequelae with focal white matter MRI abnormalities. Five children with Grade III-IV ICH had severe neurologic, cognitive, and MRI deficits, including MRI regional and diffuse white matter abnormalities and/or cortical atrophy. Focal and diffuse neurologic deficits correlated with the extent of MRI morphologic abnormalities. Results of this study indicate that ICH severity correlated with outcomes in children at follow-up; the more severe the ICH, the more adverse the neurologic, cognitive, and MRI results. MRI white matter abnormalities were present in all children with any degree ICH, while ventriculomegaly was seen only in severe ICH (Grade III-IV ICH). Neurologic deficits correlated with MRI structural abnormalities.

Brain↗

PubMed1986

Controlled trial of thyrotropin releasing hormone in amyotrophic lateral sclerosis.

A double-blind controlled trial of thyrotropin releasing hormone (TRH) 150 mg IM daily in 30 patients with amyotrophic lateral sclerosis is reported. The drug/placebo was administered for 2 months, followed by a 2-month "wash-out". Evaluation of strength, functional ability, and respiratory functions was performed. A temporary increase in the strength of some muscles was detected following the administration of TRH, but no change in functional performance was noted. Neither the patients nor the investigators believed the effects were of any marked clinical significance. The course of the illness was not altered.

Adult↗

PubMed1985