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Biomedical subjects

W T Brown

Publications and source records attributed to W T Brown.

At least 19 recordsLinked to original sources
PubMed1992

Detection of full fragile X mutation.

In fragile X syndrome, the most common inherited cause of mental deficiency, the underlying mutation is a large increase in the number of CGG repeats in a gene on chromosome X. We have developed a polymerase chain reaction (PCR) method to amplify across the full mutation in affected individuals. In this report, a fragile X family including a positive prenatally diagnosed fetus was analysed by PCR, and the results are consistent with direct genomic Southern blot analysis. Genetic screening of at-risk populations for fragile X can now be achieved by PCR rapidly, inexpensively, and on small samples.

Amino Acid Sequence↗
PubMed1992

Isolation and characterization of a highly polymorphic human locus (DXS455) in proximal Xq28.

Human Xq28 is highly gene dense with over 27 loci. Because most of these genes have been mapped by linkage to polymorphic loci, only one of which (DXS52) is informative in most families, a search was conducted for new, highly polymorphic Xq28 markers. From a cosmid library constructed using a somatic cell hybrid containing human Xq27.3----qter as the sole human DNA, a human-insert cosmid (c346) was identified and found to reveal variation on Southern blot analyses with female DNA digested with any of several different restriction endonucleases. Two subclones of c346, p346.8 and p346.T, that respectively identify a multiallelic VNTR locus and a frequent two-allele TaqI polymorphism were isolated. Examination of 21 unrelated females showed heterozygosity of 76 and 57%, respectively. These two markers appeared to be in linkage equilibrium, and a combined analysis revealed heterozygosity in 91% of unrelated females. Families segregating the fragile X syndrome with key Xq28 crossovers position this locus (designated DXS455) between the proximal Xq28 locus DXS296 (VK21) and the more distal locus DXS374 (1A1), which is proximal to DXS52. DXS455 is therefore the most polymorphic locus identified in Xq28 and will be useful in the genetic analysis of this gene dense region, including the diagnosis of nearby genetic disease loci by linkage.

Alleles↗
PubMed1992

Evidence of founder chromosomes in fragile X syndrome.

The mutation responsible for fragile X syndrome and myotonic dystrophy involves the amplification of a simple trinucleotide repeat sequence, which increases in successive generations of affected pedigrees accounting for increasing penetrance of both disorders. This common molecular basis suggests that the two diseases may share other genetic features, but whereas myotonic dystrophy exhibits a significant founder chromosome effect, fragile X syndrome apparently has a very high mutation frequency. By haplotype analysis of microsatellite markers which flank the fragile X unstable element, we have uncovered evidence of founder chromosomes of the fragile X 'mutation'. Disorders caused by heritable unstable elements may therefore exhibit common genetic properties including anticipation and founder chromosomes.

Base Sequence↗
PubMed1992

Progeria: a human-disease model of accelerated aging.

Progeria is a rare genetic disease with striking features that resemble accelerated aging. The inheritance pattern, paternal age effect, and lack of consanguinity argue that it is due to a sporadic dominant mutation. We have observed elevated levels of hyaluronic acid (HA) excretion in progeria patients. In several progeria patients we observed normal levels of growth hormone (GH) but very low levels of insulin-like growth factor I along with very high basal metabolic rates (BMRs). A trial of GH treatment was begun, which resulted in a marked increase in linear growth and a paradoxical drop in BMRs in these two patients. We hypothesize that the failure of patients with progeria to thrive may be due to a bioinactive form of GH and a lack of vasculogenesis caused by excess HA. An understanding of the progeria genetic mutation may define a key gene with a major effect on normal aging.

Basal Metabolism↗
PubMed1979

Human mutations affecting aging--a review.

A review of human genetic mutations that affect aging and their potential contribution to help understand normal aging processes is presented. The lifespans of most animal species, including man, have a genetically determined maximum. The lifespan of man appears to have evolved exceedingly rapidly, which suggests that relatively few genes may determine longevity. Analysis of biochemical evolution suggests that the regulation of enzyme levels may underlie most evolutionary changes. There is a wide spectrum of human genetic mutations. Some, such as progeria and Werner's syndrome, produce a phenotype resembling premature aging and may involve genes related to the aging process. Certain human chromosomal abnormalities, such as Down's syndrome, produce an appearance of premature aging and may be due to abnormal gene regulatory mechanisms. Progress in understanding the genetic mechanisms underlying aging is likely to come from elucidation of the molecular defects that result in the premature aging syndromes and from insights gained regarding the regulatory mechanisms governing eukaryotic genetic expression.

Aging↗
PubMed1979

A scanning electron microscope study of developing hamster tracheal epithelium in organ culture.

The ultrastructural surface features of tracheal epithelium at various times of development in organ culture were compared with those in the trachea of Syrian golden hamsters of similar age using scanning electron microscopy. Whole tracheal organ cultures, prepared from 3-day-old hamsters, were maintained in HEPES buffered CMRL 1066 medium with 0.2% bovine serum albumin. The ventral epithelial surface of trachea from 3-day-old animals was characterized by numerous microvillous cells, occasional well-developed cilia, and cells containing short cilia representing various stages of ciliary differentiation. After seven days in culture, an increased number of ciliated cells as well as developing cilia were seen. The epithelium after 14 days in culture appeared to have equal numbers of ciliated and microvillous cells, a pattern strikingly similar to that observed in vivo. After 21 days in culture, groups of well-developed cilia were interspersed with nonciliated cells covered with short, poorly developed surface microvilli. A similar pattern was found in the trachea of comparable age (24 days), with the exception of the microvillous cells; many being dome-shaped containing cluster of microvilli with prominent outlines. The tracheal organ culture, as developed in this investigation, appears to represent an excellent model for studying age-related effects of toxic and infectious agents on ciliated epithelial cells.

Age Factors↗
PubMed1978

Changing manifestations of brown tumors on bone scan in renal osteodystrophy.

In a patient with chronic renal failure and secondary hyperparathyroidism, brown tumors, visualized initially as photon-deficient areas on bone scintigraphy, reverted to areas of abnormally increased activity following parathyroidectomy. This dual appearance on bone scan paralleled the functional state of the parathyroid gland. The possible relationship of hyperhosphatemia to the increased bone-scan activity noted in the calvarium, mandible, and facial bones is discussed.

Adult↗
PubMed1977

Unit responses in the frog's caudal thalamus.

Single unit microelectrode recordings were made in the caudal thalamic region of the frog, Rana pipiens, from a sample of multimodal sensory units which included monocular, binocular, tactile, and spontaneous types, and which showed a wide variety of receptive field sizes, response rates, preferred stimulus sizes habituation rates, and velocity and tactile sensitivities. A number of special response properties were occasionally observed, including directional sensitivity, stationary object sensitivity, afterdischarges, and visual and tactile inhibitory fields. Computer analysis of spontaneously active units revealed four types: regular, exponential, bursting, and multimodal.

Animals↗
PubMed1977

Follow-up technetium-99m stannous pyrophosphate myocardial scintigrams after acute myocardial infarction.

Technetium-99m stannous pyrophosphate (99mTc-PYP) myocardial scintigrams were obtained in 68 patients during acute myocardial infarction (AMI) and at follow-up 15.9 +/- 8.8 weeks later. All patients with AMI had a positive scintigram (2+ or greater); only one of 46 control patients (2%) had a positive (2+) scintigram. At follow-up scintigraphy 6 to 37 weeks following AMI, 57% of patients had a persistently positive scintigram even though recurrent AMI was suspected in only one of these patients. Patients with persistently positive scintigrams tended to have more severe disease as evidenced by compensated congested heart failure (41%) persistent angina (77%), and ECG evidence of ventricular dyssynergy (51%), We conclude that 1) in patients with prior AMI, a 2+ abnormality on 99mTc-PYP scintigram may not represent new AMI; 2) a persistently positive 99mTc- PYP scintigram may have prognostic implications since it occurs predominantly in patients with severe symptomatic coronary disease.

Acute Disease↗
PubMed1976

Emergency management of the injured child.

Now that the crisis situation is past and the child appears to be stable, do not be lulled into a sense of security. Repeated examinations will be necessary to uncover significant internal injuries, such as a subcapsular hematoma of the spleen or liver that gives rise to continuous slow bleeding and may not show signs or symptoms until several hours after the time of injury. the first chest film may be within normal limits. A film several hours later may show the characteristic infiltrates of pulmonary contusion. Arterial blood gases may change before demonstrating other physical signs or symptoms of metabolic or respiratory deficiencies. The primary physician who cares for the multiply injured child must be familiar with the special needs of infants and children. They are not little adults. Dosages of medications differ; these children have special needs to meet for growth and development, and special psychologic needs. In dealing with the very young, do not give up too soon, especially with central nervous system injury. Many of these children have the ability to make a ""miraculous'' recovery, with little or no residual damage. I would like to make a special plea for the early use of hyperalimentation solution in the treatment of the multiple injury as a means of promoting optimum growth, development, and healing of the injured child.

Amylases↗