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Biomedical subjects

G N Wilson

Publications and source records attributed to G N Wilson.

At least 73 records · Page 4Linked to original sources
PubMed1986

Zellweger syndrome: diagnostic assays, syndrome delineation, and potential therapy.

Patients with the cerebrohepatorenal syndrome of Zellweger lack peroxisomes and certain peroxisomal enzymes such as dihydroxyacetone phosphate acyltransferase in their tissues. Deficiency of this enzyme, which is necessary for glycerol ether lipid synthesis, provides a biochemical method for recognizing patients with subtle manifestations of Zellweger syndrome and suggests the utility of exogenous ether lipid precursors as a therapeutic strategy for these children. We describe the results of glycerol ether lipid supplementation to two children, one with classic Zellweger syndrome and 9% of control fibroblast dihydroxyacetone phosphate acyltransferase activity, and one with mild facial manifestations, wide sutures, hypotonia, developmental delay, hepatomegaly, peripheral retinal pigmentation, and 50% of control fibroblast dihydroxyacetone phosphate acyltransferase activity. An increase in erythrocyte plasmalogen levels following therapy was clearly demonstrated in the milder patient, and neither patient showed evidence of toxicity. Evaluation of therapy by comparison to the usual clinical course of Zellweger syndrome was not helpful because of the variability and incomplete documentation of 90 previously reported cases. The literature survey did provide criteria for classic Zellweger syndrome, which include hypotonia with or without deformation of limbs, large fontanels and split sutures, prominent forehead, flattened facial profile with hypoplastic supraorbital ridges, anteverted nares, highly arched palate, cryptorchidism or labial hypoplasia, hepatomegaly or elevated liver enzymes, peripheral pigmentation of the retina, renal cortical cysts, and characteristic neuropathology involving decreased myelinization, abnormal neuronal migration, and sudanophilic macrophages. Less severe patients, as exemplified by our case 2 and others from the literature, will not have all the classic features and can be recognized only by a growing panel of biochemical indicators. Our patient studies illustrate the complexity of designing comprehensive therapy for Zellweger-like conditions, suggest other diseases that may involve peroxisomal alterations, and emphasize the need for multicenter, collaborative studies to evaluate biochemical heterogeneity and therapy of peroxisomal disorders.

Adrenoleukodystrophy↗
PubMed1986

Occurrence of holoprosencephaly in chromosome 13 disorders cannot be explained by duplication/deficiency of a single locus.

Four cases of holoprosencephaly with duplication/deletion involving chromosome 13 are presented and additional cases are summarized from the literature. When examined as a series, the duplications (trisomy 13, trisomy 13pter----q14) and deletions (deletion 13q12----qter, deletion 13q31----qter, ring 13 with deletion 13q14----qter) exclude deletion or duplication of single chromosome 13 bands as the cause for holoprosencephaly. Increased dosage of the 13pter----q14 region relative to the 13q14----qter region as the cause is also ruled out by the duplication 13q21----qter cases reported in the literature. Altered timing of forebrain development, causing reversion to a more primitive embryonic and phylogenetic brain structure, is related to dosage imbalance of at least two chromosome 13 regions.

Chromosome Aberrations↗
PubMed1986

Improved growth of human urothelial carcinoma cell cultures.

From January, 1981 through June, 1982 specimens from 21 patients with bladder (urothelial) cancer were placed in tissue culture, and one long term cell line was established (5%). From July, 1982 through February, 1984, using an improved culture medium, seven long term cell cultures were established from 21 patients (33%). In addition, one long term culture from a patient with a bladder melanoma was established using the standard culture medium. The nine cell cultures were derived from the following types of tumors: transitional cell carcinoma (6), adenocarcinoma (1), squamous cell carcinoma (1) and melanoma (1). All of the cell lines have produced tumors in athymic nude mice except for one transitional cell carcinoma. All of the cultures demonstrate aneuploidy. Homogeneously staining regions have been seen in some cell cultures. A common marker chromosome has not been identified.

Aneuploidy↗
PubMed1986

Detection of neural tube defects with alpha-fetoprotein measurement in amniotic fluid. A protocol for managing elevated values.

The clinical efficacy of rocket immunoelectrophoresis (RIE) and radioimmunoassay (RIA) methods for the measurement of amniotic fluid alpha-fetoprotein (AFP) were compared in separate series of over 1,000 pregnancies each. Using a mean +3 SD limit, 21 of 1,414 pregnancies monitored with RIE and 21 of 1,006 monitored with RIA were interpreted as having borderline elevated values. Five of the elevated AFP values in each series represented abnormal fetuses. No neural tube defects went undetected, although one was recognized only with ultrasound. Only two of seven abnormal fetuses had a family history of neural tube defects, indicating that maternal serum AFP measurement is an important preventive measure in pregnancies that are not recognized as at high risk. The data support the use of commercially available RIA kits for amniotic fluid AFP measurement and suggest a protocol for management of elevated values.

Amniotic Fluid↗
PubMed1985

The phenotypic and cytogenetic spectrum of partial trisomy 9.

A new patient with trisomy for the chromosome segment 9pter----q22 is compared to 19 previously reported cases of partial trisomy 9. Manifestations such as microcephaly, prominent nasal root, bulbous nose, and down-turned corners of the mouth are common to patients with trisomic segments extending from 9p21 to 9q13, while intra-uterine growth retardation, cleft lip/palate, skeletal anomalies, and heart defects are more common with trisomic segments extending through 9q22-9q32. A graphic method illustrates this progression in the partial trisomy 9 malformation spectrum as the triplicated chromosome region extends from bands 9p21 to 9q32. More severe and random defects are observed with complete trisomy 9 or tetrasomy 9p, suggesting an extreme excess of material greatly increases developmental variability.

Abnormalities, Multiple↗
PubMed1985

Further delineation of the dup(3q) syndrome.

Three patients with duplication of 3q regions ranging from 3q25----qter to the entire long arm provide additional documentation of the dup(3q) malformation syndrome. Data on 40 cases now reported define a characteristic face with hirsutism, synophrys, broad nasal root, anteverted nares, downturned corners of the mouth, micrognathia, and malformed ears recognizable even in the 30-week fetus and distinct from that of the Brachmann-de Lange syndrome. Other characteristic anomalies include congenital heart anomalies involving primarily septal defects, hand malformations including simian creases, abnormal dermatoglyphics, clinodactyly or camptodactyly, omphalocele, skeletal anomalies, and genitourinary malformations. Severe mental and growth retardation are common in those patients (64%) who survive the first year. Chromosome study of relatives is extremely important for counseling because only 10 of 40 cases represented de novo duplications.

Abnormalities, Multiple↗
PubMed1985

Phenotypic delineation of ring chromosome 15 and Russell-Silver syndromes.

A male child with features of the Russell-Silver syndrome, including pre- and postnatal growth delay, triangular facies, bilateral fifth finger clinodactyly, and disproportionate lower extremities, was found to have a ring chromosome 15 in all peripheral leucocytes examined. Review of the reported cases of ring chromosome 15 defines a malformation syndrome with a characteristic facies related to deletion of the 15q26.2----qter region. Russell-Silver and ring 15 syndromes share clinical features such as growth deficiency, triangular facies, digital anomalies, and café-au-lait spots. Microcephaly, mental retardation, facial dysmorphology, limb anomalies, and cardiac defects are more striking in ring chromosome 15 patients and are indications for karyotyping when found in conjunction with the Russell-Silver phenotype.

Chromosome Aberrations↗
PubMed1985

Delayed developmental sequences in rodent diabetic embryopathy.

Diabetes induced by alloxan at day 6 of gestation in Wistar rats produced decreased fetal growth, delayed skeletal ossification, decreased fetal kidney beta-glucuronidase, and an increased frequency of fetal birth defects which correlated with the degree of diabetic control. Offspring of severely diabetic mothers (mean blood glucose greater than 501 mg/dl) sacrificed at 20 days had a mean weight of 2.12 +/- 0.16 g, a mean of 1.8 +/- 0.46 caudal ossification centers, and a 28% incidence of birth defects as compared to 3.70 +/- 0.22 g, 5.9 +/- 0.42 caudal centers, and 1.1% defects for controls. Offspring of severely diabetic mothers sacrificed at 21 days had mean numbers of caudal and sternal ossification centers which did not significantly differ from controls, indicating that decreased ossification observed at 20 days of gestation is a delayed developmental sequence which is mostly corrected by 21 days. Offspring of moderately diabetic (mean blood glucose 300-500 mg/dl) and insulin-treated dams (mean blood glucose 152-168 mg/dl) had intermediate degrees of growth or ossification delay and birth defect frequency at both the 20- and 21-day sacrifices. Maternal diabetes also retards the developmental increase in fetal kidney beta-glucuronidase such than 20-day offspring of severely diabetic mothers had a mean specific activity of 1.1 nmol/min/mg compared to 3.0 nmol/min/mg for controls. The results support prior studies in rodents suggesting a progression of early growth delay, altered developmental sequences, and birth defects in diabetic pregnancy. This progression is suggested as a common teratogenic mechanism which has implications for evaluating analogous pregnancies in man.

Animals↗
PubMed1984

Deficiency of enzymes catalyzing the biosynthesis of glycerol-ether lipids in Zellweger syndrome. A new category of metabolic disease involving the absence of peroxisomes.

The Zellweger cerebro-hepato-renal syndrome is a genetic disease characterized by the absence of peroxisomes and deficiency of glycerol-ether lipids in several tissues. We measured the activity of dihydroxyacetone phosphate (DHAP) acyltransferase, a peroxisomal enzyme with a major role in ether lipid synthesis, in fibroblasts and leukocytes from patients with Zellweger syndrome. Control skin and amniotic-fluid fibroblasts had normal activity of DHAP acyltransferase (0.28 to 0.3 nmol per minute per milligram of protein), whereas fibroblasts from three patients with Zellweger syndrome had deficient activity (0.013 +/- 0.006 nmol per minute per milligram of protein). The activity of the enzyme in leukocytes and levels of plasmalogens (the major class of cellular glycerol-ether lipids) in erythrocytes were also deficient in a patient, but normal levels of leukocyte enzyme and erythrocyte plasmalogens were found in her parents. Other enzymes of the acyl DHAP pathway exhibited alterations in fibroblasts from patients with Zellweger syndrome, and the activity of the glycerophosphate acyltransferase was also reduced. These results support prior studies emphasizing the role of peroxisomes and the acyl DHAP pathway in cellular ether lipid synthesis, establish Zellweger syndrome cells as valuable for elucidating peroxisomal functions, and provide prenatal and postnatal diagnostic assays as well as potential therapeutic strategies for Zellweger syndrome.

Acyltransferases↗
PubMed1984

Individual and evolutionary variation of primate ribosomal DNA transcription initiation regions.

A 16-kilobase region surrounding the transcription initiation site for ribosomal DNA and including the entire ribosomal DNA transcription unit has been characterized in man and compared in higher primates. Restriction analysis of ribosomal DNA from the pygmy chimpanzee (Pan paniscus), the common chimpanzee (Pan troglodytes), the gorilla (Gorilla gorilla), the orangutan (Pongo pygmaeus), the gibbon (Hylobates lar), and the rhesus monkey (Macaca mulatta) allows a primate phylogeny to be constructed based on ribosomal DNA structure. Individual variation and methylation are demonstrated in the ribosomal DNA repeats of all primates examined. Restriction analysis with HincII endonuclease suggests cleavage at sites containing methylated CpG and adds the SalI/HincII pair to those enzymes useful for studying DNA modification.

Animals↗
PubMed1984

Cat eye syndrome owing to tetrasomy 22pter leads to q11.

A case of tetrasomy 22pter leads to q11 with ocular hypertelorism, downward slanting palpebral fissures, total anomalous pulmonary venous return, and anal atresia is described. The phenotypic variability of the cat eye syndrome is emphasised along with the need for categorisation of these patients according to well characterised cytogenetic findings.

Abnormalities, Multiple↗
PubMed1983

Cranial defects in the Goldenhar syndrome.

Four patients are presented with the Goldenhar syndrome (GS) and cranial defects consisting of plagiocephaly, microcephaly, skull defects, or intracranial dermoid cysts. Twelve cases from the literature add hydrocephalus, encephalocele, and arhinencephaly to a growing list of brain anomalies in GS. As a group, these patients emphasize the variability of GS and the increased risk for developmental retardation with multiple, severe, or unusual manifestations. The temporal relation of proposed teratogenic events in GS provides an opportunity to reconstruct biological relationships within the 3-5-week human embryo.

Brain↗
PubMed1983

Holoprosencephaly in infants of diabetic mothers.

We report seven infants of diabetic mothers, affected with holoprosencephaly malformation sequence. An additional 15 cases assembled from personal communications and the literature indicate that holoprosencephaly, like neural tube, cardiac, and caudal defects, is specifically increased in children of diabetic mothers. Incidence figures from newborn surveys demonstrate a risk for holoprosencephaly in infants of diabetic mothers comparable to the 1% risk for caudal regression malformation sequence. The embryologic timing of cranial, cardiac, and caudal defects emphasizes the need for pregnancy planning and diabetes control.

Abnormalities, Multiple↗
PubMed1983

Partial trisomy 2q.

An infant with unusual facies and anomalies of brain, heart, and kidney was found to have a simple duplication of the distal long arm of chromosome 2. The clinical features of this case refine the phenotypic spectrum of partial trisomy 2q; prior cases had more complicated chromosomal rearrangements.

Abnormalities, Multiple↗