Biomedical subjects
J G Hall
Publications and source records attributed to J G Hall.
Twinning: mechanisms and genetic implications.
In the past, twins have been studied to determine the genetic contribution to various disease processes. Recent work, however, suggests that monozygotic (MZ) twins are not truly identical. Many genetic forms of discordance have been described within MZ twin pairs and may even play a role in causing MZ twinning. Intra-uterine environmental differences in the allocation of the number of cells and in the placental vascular supply to each twin, as well as stochastic development events, may lead to major discordance at birth between the twins of a MZ pair.
Embryologic development and monozygotic twinning.
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An introduction to genomic imprinting and parent of origin effects.
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Multifactorial inheritance of non-syndromic macrocephaly.
OBJECTIVE: To reevaluate previous claims that non-syndromic macrocephaly is usually inherited as an autosomal dominant trait. DESIGN: Head size was measured in the parents and sibs of children with non-syndromic macrocephaly. OUTCOME MEASURES: If autosomal dominant inheritance is involved, the frequency distribution should be bimodal. RESULTS: Head circumference of parents and sibs of the macrocephalic probands had a mean significantly greater than the population norm, and a unimodal distribution. Probands with psychomotor impairment had bigger heads, and more had a history of birth difficulty, than did unimpaired probands. CONCLUSIONS: The usual genetic basis for non-syndromic macrocephaly is multifactorial with a polygenic genetic basis, rather than autosomal dominant. Risk of recurrence appears to be much lower than if it would be on the assumption of autosomal dominant inheritance. Macrocephaly in a parent or sib of an unborn child may present a risk for birth injury to that child. A larger series of patients will be necessary to resolve this question.
Differentiation of bacterial 16S rRNA genes and intergenic regions and Mycobacterium tuberculosis katG genes by structure-specific endonuclease cleavage.
We describe here a new approach for analyzing nucleic acid sequences using a structure-specific endonuclease, Cleavase I. We have applied this technique to the detection and localization of mutations associated with isoniazid resistance in Mycobacterium tuberculosis and for differentiating bacterial genera, species and strains. The technique described here is based on the observation that single strands of DNAs can assume defined conformations, which can be detected and cleaved by structure-specific endonucleases such as Cleavase I. The patterns of fragments produced are characteristic of the sequences responsible for the structure, so that each DNA has its own structural fingerprint. Amplicons, containing either a single 5'-fluorescein or 5'-tetramethyl rhodamine label were generated from a 620-bp segment of the katG gene of isoniazid-resistant and -sensitive M. tuberculosis, the 5' 350 bp of the 16S rRNA genes of Escherichia coli O157:H7, Salmonella typhimurium, Salmonella enteritidis, Salmonella arizonae, Shigella sonnei, Shigella dysenteriae, Campylobacter jejuni, staphylococcus, hominis, Staphylococcus warneri, and Staphylococcus aureus and an approximately 550-bp DNA segment comprising the intergenic region between the 16S and 23S rRNA genes of Salmonella typhimurium, Salmonella enteritidis, Salmonella arizonae, Shigella sonnei, and Shigella dysenteriae serotypes 1, 2, and 8. Changes in the structural fingerprints of DNA fragments derived from the katG genes of isoniazid-resistant M. tuberculosis isolates were clearly identified and could be mapped to the site of the actual mutation relative to the labeled end. Bland patterns which clearly differentiated bacteria to the level of genus and, in some cases, species were generated from the 16S genes. Cleavase I analysis of the intergenic regions of Salmonella and Shigella species differentiated genus, species, and serotypes. Structural fingerprinting by digestion with Cleavase I is a rapid, simple, and sensitive method for analyzing nucleic acid sequences and may find wide utility in microbial analysis.
Amyoplasia, the most common type of arthrogryposis: the potential for good outcome.
BACKGROUND: Amyoplasia is the most commonly seen diagnostic subgroup of children with arthrogryposis. The natural history of these children has not been well described previously. METHODS: Review of the medical records of 38 children with amyoplasia enabled us to describe their birth characteristics, therapeutic interventions, and functional outcomes. RESULTS: Eighty-four percent of the children had symmetrical, four-limb involvement, which was similar to the original descriptions of amyoplasia, at birth. There was an average of 5.7 orthopedic procedures per child, and the children had multiple castings and splintings of their limbs and participated in physical and occupational therapy on a regular basis. By the age of 5 years, 85% were ambulatory, most were relatively or completely independent in their activities of daily living, and most were in regular classrooms at the appropriate grade level. CONCLUSION: Although children with amyoplasia have pronounced musculoskeletal involvement at birth, which requires orthopedic and rehabilitative interventions during their childhood, their functional outcome in both physical and educational areas is excellent.
1995 ASHG presidential address. The challenges and opportunities of times of change.
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Dominant distal arthrogryposis in a Maori family with marked variability of expression.
The index case was a Maori bushman who presented with severe congenital spinal stenosis and manifestations of distal arthrogryposis. His offspring and 8 of his 9 sibs and most of their offspring were interviewed and examined. Of those examined 7 individuals with definite and 2 with probable distal arthrogryposis were identified in 4 of the families. A tenth relative with distal arthrogryposis and contractural arachnodactyly had died. There was marked variability in the severity and nature of manifestations with 2 having severe hand and foot involvement in addition to craniofacial changes compatible with a diagnosis of Freeman-Sheldon syndrome. Other apparently unrelated hereditary disorders in the family included ectrodactyly, biliary atresia, and Brachmann-de Lange syndrome. This is the first report of arthrogryposis in a Maori family.
Clinical course and systemic correlates of retinopathy of prematurity in quintuplets.
PURPOSE/METHODS: We studied clinical correlates of retinopathy of prematurity in four surviving quintuplets with similar low birth weights and gestational age of 27 weeks. Prospective serial ophthalmoscopic examinations and retrospective chart analysis were used. RESULTS/CONCLUSIONS: Retinopathy of prematurity varied among the neonates from stage 2 with total regression to threshold progressing to retinal detachment. Severity of eye disease correlated with duration of mechanical ventilation and of parenteral nutrition, as well as frequency of hypoglycemia and of hypercapnia. Poor outcome correlated inversely with weight gain.
Sarcoidosis of the eyelid skin.
PURPOSE/METHODS: A 34-year-old woman with a history of pulmonary sarcoidosis was referred for examination and treatment of suspected molluscum contagiosum nodules of the eyelids. After full ophthalmic examination, she underwent a biopsy of an eyelid nodule. RESULTS/CONCLUSIONS: Histopathologic examination of the eyelid nodule showed numerous, noncaseating granulomas as well as giant cells. This case represents the rare findings of sarcoidosis of the eyelid skin in a patient with chronic but not ocular sarcoidosis.
Information update on Achondroplasia.
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New mechanisms for genetic disease and nontraditional modes of inheritance.
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Neural tube defects in British Columbia.
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Non-traditional forms of inheritance in skeletal dysplasias.
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Mouse homologues of human hereditary disease.
Details are given of 214 loci known to be associated with human hereditary disease, which have been mapped on both human and mouse chromosomes. Forty two of these have pathological variants in both species; in general the mouse variants are similar in their effects to the corresponding human ones, but exceptions include the Dmd/DMD and Hprt/HPRT mutations which cause little, if any, harm in mice. Possible reasons for phenotypic differences are discussed. In most pathological variants the gene product seems to be absent or greatly reduced in both species. The extensive data on conserved segments between human and mouse chromosomes are used to predict locations in the mouse of over 50 loci of medical interest which are mapped so far only on human chromosomes. In about 80% of these a fairly confident prediction can be made. Some likely homologies between mapped mouse loci and unmapped human ones are also given. Sixty six human and mouse proto-oncogene and growth factor gene homologies are also listed; those of confirmed location are all in known conserved segments. A survey of 18 mapped human disease loci and chromosome regions in which the manifestation or severity of pathological effects is thought to be the result of genomic imprinting shows that most of the homologous regions in the mouse are also associated with imprinting, especially those with homologues on human chromosomes 11p and 15q. Useful methods of accelerating the production of mouse models of human hereditary disease include (1) use of a supermutagen, such as ethylnitrosourea (ENU), (2) targeted mutagenesis involving ES cells, and (3) use of gene transfer techniques, with production of 'knockout mutations'.
Neural tube defects. Introduction.
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Rapid immunofiltration assay of Newcastle disease virus using a silicon sensor.
A rapid nonradioactive sandwich immunoassay which utilizes biotin-streptavidin mediated filtration capture of immune complexes in conjunction with a silicon sensor was developed for the detection of virus. Using purified Newcastle disease virus as a model, the lower limits of detection (LOD) were determined for a number of immunoassay configurations employing both monoclonal and polyclonal antibodies. The LODs ranged from 1.3 ng/ml (sample volume of 100 microliter) for an incubation of 60 min to 400 ng/ml for a 1 min incubation. The sandwich immune complexes were formed from one-step incubation of antibody and antigen. No 'hook' effects were observed over a wide range of analyte concentrations. The assays were easy to perform and required a total time equal to the incubation period plus about 5 min. The assay format is suitable for virus, bacteria and protein antigens. New assays can be developed and optimized readily, often within 1 day.