PubMed Health⌕ Search

Biomedical subjects

L K Robinson

Publications and source records attributed to L K Robinson.

16 recordsLinked to original sources
PubMed1992

Expression of a human chimeric transferrin gene in senescent transgenic mice reflects the decrease of transferrin levels in aging humans.

Transgenic mice provide a means to study human gene expression in vivo throughout the aging process. A DNA sequence containing 668 bp of the 5' regulatory region of the human transferrin gene was fused to the bacterial reporter gene chloramphenicol acetyl transferase (TF-CAT) and introduced into the mouse genome. Expression of the human chimeric transferrin gene was similar to the tissue patterns of mouse and human transferrin. In aging transgenic mice, expression of the human chimeric transferrin gene was found to diminish 40% in livers between 18 and 26 months of age. Transferrin levels and serum iron levels in aging humans also diminish, as observed from measurements of total iron binding capacity and percent iron saturation in sera from 701 individuals ranging from 0 to 99 years of age. In contrast, in transgenic mice and nontransgenic mice, the mouse endogenous plasma transferrin and endogenous Tf mRNA increase significantly during aging. Neither the decrease of human TF-CAT nor the increase of mouse transferrin during aging appears to be part of a typical inflammatory reaction. Although the 5' regions of the human transferrin and mouse transferrin genes are homologous, sequence diversities exist which could account for the different responses to inflammation and aging observed.

Adolescent↗
PubMed1992

Pathophysiology of congenital diaphragmatic hernia. III: Exogenous surfactant therapy for the high-risk neonate with CDH.

Exogenous surfactant therapy (EST) in surfactant-deficient premature infants has been shown to improve lung compliance, decrease morbidity, and improve survival. Reports have demonstrated that newborns with congenital diaphragmatic hernia (CDH) have lung compliance, pressure-volume curves, and hyaline membrane formation resembling those changes seen in surfactant deficient premature newborns. We hypothesize that EST may also benefit infants with CDH. All high risk cases of prenatally diagnosed CDH at Children's Hospital of Buffalo from November 1988 to February 1991 were prospectively evaluated for EST. In those families who chose to participate, the surfactant preparation, Infasurf (100 mg/kg), was instilled into the newborn's lungs prior to the first breath. The remainder of the perinatal, neonatal, and surgical care was performed in a routine manner. Three high-risk prenatally diagnosed newborns with left CDH were treated with EST. All showed signs of decreased pulmonary compliance, but could still be adequately oxygenated and ventilated. Surgical correction was performed after stabilization and all required patch closures. Two of the three infants suffered no life-threatening episodes of pulmonary hypertension and all survived. These infants had many known indicators for poor outcome in CDH with an expected survival of less than 20%. We believe that EST in these neonates with CDH contributed to their survival with minimum morbidity. These results suggest that surfactant replacement for the high-risk neonate with CDH warrants further consideration and a randomized clinical trial is being planned.

Adult↗
PubMed1990

Human transferrin. Expression and iron modulation of chimeric genes in transgenic mice.

Transferrin (TF) is a plasma protein that transports and is regulated by iron. The aim of this study was to characterize human TF gene sequences that respond in vivo to cellular signals affecting expression in various tissues and to iron administration. Chimeric genes were constructed containing 152, 622, and 1152 base pairs (bp) of the human TF5'-flanking region with the coding region of a reporter gene, CAT (chloramphenicol acetyltransferase), and introduced into the germ line of mice. Transgenes containing TF 5'-flanking sequences to -152 bp were expressed poorly in all tissues examined. In contrast, transgenes containing TF sequences to -622 or -1152 bp were expressed at high levels in brain and liver, greater than or equal to 1000-fold higher than tissues such as heart and testes. Liver and brain are major sites of endogenous TF mRNA synthesis, but liver mRNA levels are 10-fold higher than brain. A significant diminution of CAT enzymatic activity in liver accompanied iron administration in both TF(0.67) and TF(1.2)CAT transgenic mice, mimicking the decrease of transferrin in humans following iron overload. Levels of endogenous plasma transferrin also decreased in iron-treated transgenic mice. Transgenic mouse lines carrying human TF chimeric genes will be useful models for analyzing the regulation of human transferrin by iron and for determining the molecular basis of transferrin regulation throughout mammalian development into the aging process.

Animals↗
PubMed1990

Prenatal diagnosis of skeletal dysplasia identified postnatally as hypochondroplasia.

A short-limb skeletal dysplasia was diagnosed prenatally at 35 weeks of gestation. After birth the infant was found to have hypochondroplasia. The parents are of average stature, and the child's disorder presumably occurred as a fresh mutation. This appears to be the first reported case of hypochondroplasia diagnosed prenatally as a "non-specific skeletal dysplasia" in the absence of a family history. Evaluation after birth showed that the infant, whose parents are of normal stature, has hypochondroplasia.

Female↗
PubMed1990

Prenatal cocaine exposure and fetal vascular disruption.

The question of the potential teratogenicity of cocaine has been raised by the increasing frequency of its abuse in the United States. In previous studies, an increased incidence has been documented of spontaneous abortion, placental abruption, prematurity, intrauterine growth retardation, and neurologic deficits in the infants of women who abused cocaine. More recently, it has been suggested in studies that fetal vascular disruption accompanying maternal cocaine abuse may lead to cavitary central nervous system lesions and genitourinary anomalies. In this article, 10 children born of women who abused cocaine are described, 9 of whom have congenital limb reduction defects and/or intestinal atresia or infarction. The spectrum of anomalies associated with embryonic and fetal vascular disruption accompanying maternal cocaine abuse is thus enlarged. The specific risk for congenital anomalies accompanying maternal cocaine abuse during an individual pregnancy is unknown. However, data from these patients and the available literature suggest that counseling pregnant women concerning cocaine use should incorporate warnings about the possibility of associated embryonic or fetal vascular disruption.

Abnormalities, Drug-Induced↗
PubMed1989

Characterization of a novel glycoprotein isolated from the basement membrane matrix of the Engelbreth-Holm-Swarm tumor.

A previously undescribed protein has been isolated and purified from the extracellular matrix of the Engelbreth-Holm-Swarm (EHS) tumor, a murine tumor that synthesizes an extensive matrix composed of basement membrane molecules. Molecular characterization of the molecule determined that it is a glycoprotein with internal disulfide bonds and an isoelectric point of 6.0. Electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the glycoprotein migrated as a diffuse band with a molecular weight of approximately 72,000-80,000. The amino acid composition was significantly different from known basement membrane components. Polyclonal antibodies that specifically recognize the glycoprotein localized it to the kidney glomerular basement membrane. These antibodies did not cross-react with either known basement membrane components (laminin, type IV collagen, and heparan sulfate proteoglycan), with 70K "culture shock" protein or with components of normal mouse serum (including mouse transferrin, albumin, or alpha-fetoprotein), when analyzed by "Western" immunoblots. Our data indicate that the glycoprotein is synthesized by the EHS tumor cells and is present at relatively high levels in the EHS tumor matrix.

Amino Acids↗
PubMed1989

Severe perinatal Marfan syndrome.

The cardiovascular manifestations of the Marfan syndrome in older children and adults have been well described. Clinical, radiographic, and echocardiographic data regarding three patients with severe perinatal Marfan syndrome are described. Two of these patients had the syndrome at birth and died in infancy. The syndrome was diagnosed in the third patient at 6 months of age and the child is still alive at 3 years of age. The possible relationship among the Marfan syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta is considered. Patients with Marfan syndrome and severe cardiorespiratory problems early in life tend to have a limited life expectancy.

Acute Disease↗
PubMed1988

Congenital optic atrophy and brachytelephalangy: the Berk-Tabatznik syndrome.

Here we report on a prepubertal boy with the Berk-Tabatznik syndrome. Manifestations included short stature, congenital optic atrophy, and hypoplasia of the cervical vertebral bodies and distal phalanges. Prognosis was adversely affected by visual and auditory difficulties. The cause of this condition remains unknown.

Deafness↗
PubMed1987

Vascular pathogenesis of unilateral craniofacial defects.

The term hemifacial microsomia refers to unilateral defects in development of structures derived from the first and second branchial arches. Recently we evaluated three unrelated children who had a similar pattern of unilateral craniofacial defects that was associated with other structural abnormalities having a disruptive vascular pathogenesis. The clinical findings in these patients suggest that one cause of hemifacial microsomia is in utero interruption of blood flow.

Adolescent↗
PubMed1987

Multiple pterygium syndrome: a case complicated by malignant hyperthermia.

The autosomal recessive multiple pterygium syndromes are a heterogeneous group of disorders in which multiple joint contractures are associated with cutaneous webbing. Recently, we evaluated a 33 week gestation male in whom multiple pterygia were one feature of a broader pattern of malformation. Clinical management was adversely affected by malignant hyperthermia. In this report we present the clinical, radiographic and pathologic data of this patient and those of an affected stillborn female sibling. We believe that these represent the features of a newly recognized disorder.

Abnormalities, Multiple↗
PubMed1985

Carpenter syndrome: natural history and clinical spectrum.

Recently, we evaluated three sibs with Carpenter syndrome, permitting further clinical, orthopedic, radiographic, and psychometric delineation of this disorder. All three patients were operated on for craniostenosis at or before 2 months. Although all had gross motor delay in early infancy, two had normal intelligence at 12 months and 10 years, respectively. Bony abnormalities contributed to functional impairment especially in the older children. Preaxial polydactyly of feet was present in all three affected sibs and in all other reported individuals with this condition, allowing differentiation of Carpenter syndrome from the other autosomal-recessive acrocephalopolysyndactyly syndromes.

Adolescent↗
PubMed1985

Brachmann-de Lange syndrome: evidence for autosomal dominant inheritance.

We have evaluated a family in whom a mildly affected mother and her two severely affected sons have manifestations of the Brachmann-de Lange syndrome suggesting that some cases of this disorder are inherited in an autosomal dominant fashion. Documentation of the clinical phenotype in two generations of this family permits further delineation of the phenotypic spectrum of the disorder. The fact that most affected patients represent sporadic cases in otherwise normal families might represent the inability of severely affected individuals to reproduce.

Adult↗