Biomedical subjects

W R Williams

Publications and source records attributed to W R Williams.

9 recordsLinked to original sources

PubMed1992

The Li-Fraumeni syndrome: from clinical epidemiology to molecular genetics.

The goal of this review is to demonstrate the effective interaction of epidemiologic methods and molecular genetics in the identification of familial cancer predisposition. The example involves a hospital-based population of childhood soft tissue sarcoma patients who were less than age 16 years at diagnosis at the University of Texas M. D. Anderson Cancer Center, Houston, Texas, in 1944 through 1976, had survived at least 3 years from diagnosis, and were diagnosed at least 5 years before the start of our study. Familial data were collected on the patients' offspring, full siblings, parents, aunts, uncles, and grandparents. The initial analysis revealed a small but significant cancer excess in first-degree relatives. Genetic analysis demonstrated that the cancer distribution in families could best be explained by a rare autosomal dominant gene with penetrance such that the risk of cancer by age 35 years was nearly 50%. Most of the evidence for a dominant gene came from nine kindreds. Laboratory investigation of fibroblasts from those kindreds provided an in vitro model of cellular immortalization and carcinogenesis. Germline mutations in the tumor suppressor gene p53 were found in two of the families, and studies are ongoing in the other kindreds. This review demonstrates the power of genetic epidemiologic methods to characterize statistically a cancer-predisposing gene and the application of molecular genetics to define the genetic defect.

Adolescent↗

PubMed1992

In vitro displacement of vasoactive mediators from plasma proteins: a possible mechanism for pseudo-allergic reactions to neuromuscular blocking drugs.

We have studied the release of prostaglandin F2 alpha (PGF2 alpha) and histamine from serum proteins by neuromuscular blocking drugs using equilibrium dialysis, with tracer quantities of radio-labelled mediators as probes. Small concentrations (0.05-0.25 mmol litre-1) of competitive neuromuscular blocking drugs displaced 16-67% of bound histamine. Greater concentrations of suxamethonium (2 mmol litre-1) were required for histamine displacement (19%). There was a significant release of PGF2 alpha by atracurium 1 mmol litre-1 and pancuronium 0.69 mmol litre-1. These findings suggest an alternative mechanism of histamine release by neuromuscular blocking drugs which may be relevant to adverse reactions during use.

Blood Proteins↗

PubMed1992

Sensitivity of Salmonella typhimurium TA97a to the type of agar used for preparation of Vogel-Bonner plates.

Recent problems with the supply of Difco bacto agar have forced some laboratories to evaluate alternative agars for use in the Salmonella/microsome assay. This led to the independent observation in two laboratories (Boots and Glaxo) that Salmonella typhimurium TA97a is sensitive to certain types of agar that may be used to prepare Vogel-Bonner minimal medium plates. A programme of work was, therefore, undertaken to investigate this phenomenon; 9-aminoacridine hydrochloride (at Boots) and 4-nitro-o-phenylenediamine (at Glaxo) were tested against TA1537 and TA97a using Vogel-Bonner plates prepared with a number of different agars. Three agars (Lab M, Difco Bi-tek and Beckton Dickinson granulated) were identified which, although supporting normal growth of TA1537 revertant colonies, gave much reduced control counts and responses to the mutagens with TA97a. One agar, Becton Dickinson grade A, gave poor responses with TA1537 but produced satisfactory results with TA97a. In contrast to the Vogel-Bonner plates, varying the type of agar used in the top agar overlays had little effect on the responses obtained. On the basis of these comparisons, Becton Dickinson purified agar was selected as a suitable alternative to Difco bacto and it was concluded that laboratories using agars other than these, or purchasing pre-poured plates without specifying the type of agar, should be made aware of potential problems with TA97a.

Agar↗

PubMed1992

Segregation analysis of cancer in families of childhood soft-tissue-sarcoma patients.

This paper presents the analysis of familial cancer data collected in a hospital-based study of 159 childhood soft-tissue-sarcoma patients. Two different statistical models detected excess aggregation of cancer, which could be explained by a rare dominant gene. For each kindred, we estimated the probability of the observed cancer distribution under the dominant-gene model and identified 12 families that are the most likely to be segregating the gene. Two of those families have confirmed germ-line mutations in the p53 tumor-suppressor gene. The relative risk of affection for children who are gene carriers was estimated to be 100 times the background rate. Females were found to have a slightly higher age-specific penetrance, but maternal and paternal lineages made equal contributions to the evidence in favor of the dominant gene. The proband's histology, ethnicity, and age at diagnosis were evaluated to determine whether any of these altered the probability of affection in family members. Only embryonal rhabdomyosarcoma was found to be a significant covariate under the dominant-gene model. While molecular genetic studies of familial cancer will eventually provide answers to the questions of genetic heterogeneity, age- and site-specific penetrance, mutation rates, and gene frequency, information from statistical models is useful for setting priorities and defining hypotheses.

Adolescent↗

PubMed1979

The likely region of overlap (LRO) method for physical assignment of loci.

Numerical analysis is applied to physical assignments of loci, providing point estimates, an LRO confidence interval, and a chi(2) test of consistency whether there is a smallest region of overlap (SRO) or not. Results are given for two examples and summarized for 81 loci in man.

Chromosome Mapping↗

PubMed1979

Morphological findings in idiopathic calcification of the ascending aorta and aortic valve affecting a young woman.

The pathology of a case of idiopathic calcification affecting the ascending aorta in a young woman is presented. A varying width of media throughout the aorta and extending into its proximaques of calcium, found in the acellular media, were confined to the ascending aorta. No inflammatory or reparative reaction was seen in the vessel wall. Electron microscopically, the calcium seemed to have an affinity for elastic tissue elements of all sizes and the mode of deposition appeared to be by 'avenues' of the microfibrillar component. Possible pathogenetic mechanisms are discussed.

Adolescent↗

PubMed1978

The hypothenar radial arch and parathenar loop in palmar dermal topology: sex, bimanual and regional variation in samples from the British Isles.

Consideration is given to the regular recording of parathenar distal loops (Pa) and hypothenar radial arches (Ar) in palmar dermal topology. Frequencies are given for four British populations (the North Pennine Dales, the Mid Welsh Borderland, Pembrokeshire and Ireland) and regional variation noted together with sex and bimanual differences. Both Pa and Ar occur infrequently in normal populations, generally in less than 5% of individuals, Pa significantly less than Ar. Both attributes are similar in that they are significantly more common on right than left hands and in females than males. Three out of twelve comparisons between the North Pennine Dales, Welsh Borderland and Pembrokeshire data attained formal significance, in each case in the males. The former two regions were distinguished for both Pa and Ar; the latter two for Ar. This is more than expected by chance at the 5% level.

Dermatoglyphics↗

PubMed1977

Mercury levels in freshwater fish of the state of South Carolina.

Samples of fish from freshwater sources of rivers, lakes and ponds all over the state of South Carolina were collected during the Summer of 1974 and 1975. The fish collected were Bass, Bluegill, Redbreast, Catfish, Shad, Carp, Crappie, Mudfish and Pike. Samples were analyzed using the flameless atomic absorption procedure outlined by Hatch and Ott, and Uthe et al as modified for use with Perkin-Elmer, Coleman MAS-50 mercury analyzer. Triplicate samples of fish tissue were analyzed by wet digestion method. The mean mercury levels in ppb were determined for baseline mercury levels. A significant finding of this report is that those species for which fish of widely differing weights were analyzed, larger fish had higher mercury levels. Mercury levels exceeding the U.S. Food and Drug Administration guideline of 500 ppb for fish tissues have been found in the Mudfish from Edisto River and Pike fish from Lake Murray. Higher levels of mercury occurred in the highly vascularized blood tissues of liver and kidney than in muscle. Carnivorous and bottom-feeding fishes are the most reliable indicators of mercury pollution.

Animals↗

PubMed1977

Reflex sympathetic dystrophy.

This paper describes a patient with typical post-traumatic Sudeck's atrophy of the right foot, who subsequently developed an atraumatic, painful osteoporosis of the left foot and right knee. It is suggested that cases of 'migrating osteolysis' and 'transient osteoporosis' of the lower limbs be grouped with classical Sudeck's atrophy as a reflex sympathetic dystrophy; Theories of pathogenesis have been reviewed and a possible theory of causation in atraumatic cases is presented.

Diagnosis, Differential↗