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E D Williams

Publications and source records attributed to E D Williams.

At least 181 records · Page 10Linked to original sources
PubMed1986

Lack of inactivation of a mouse X-linked gene physically separated from the inactivation centre.

Previous evidence had shown that, when a mammalian X-chromosome is broken by a translocation, only one of the two X-chromosome segments shows cytological signs of X-inactivation in the form of late replication or Kanda staining. In the two mouse X-autosome translocations T(X;4)37H and T(X;11)38H the X-chromosome break is in the A1-A2 bands; in both, the shorter translocation product fails to exhibit Kanda staining. By in situ hybridization, the locus of ornithine carbamoyltransferase (OCT) was shown to be proximal to the breakpoint (i.e. on the short product) in T37H and distal to the breakpoint in T38H. Histochemical staining for OCT showed that in T38H the locus of OCT undergoes random inactivation, as in a chromosomally normal animal, whereas in T37H the OCT locus remains active in all cells. The interpretation is that, when a segment of X-chromosome is physically separated from the X-inactivation centre, it fails to undergo inactivation. This point is important for the understanding of the mechanism of X-inactivation, since it implies that inactivation is a positive process, brought about by some event that travels along the chromosome. It is also relevant to the interpretation of the harmful effects of X-autosome translocations and the abnormalities seen in individuals carrying such translocations.

Animals↗
PubMed1986

Prolongation of fibroblast life span associated with epithelial rat tumor development.

We have examined the proliferative behavior in culture of stromal cells of fibroblast morphology taken from various stages in the development of experimentally induced epithelial tumors in the rat thyroid. In this model long-term stimulation by an elevated level of serum thyroid stimulating hormone leads first to hyperplasia, then to multiple benign, and finally malignant tumors. Fibroblasts from hyperplastic glands, despite having already undergone more divisions in vivo, consistently showed a longer life span than normal fibroblasts in culture, averaging 16 compared with six divisions before senescing. In the three tumor bearing glands studied, all cultures have undergone more than 40 divisions (in one case over 70) and none has yet shown signs of senescence. We conclude that the life span of thyroid fibroblasts observed in culture has been reset to a higher limit by growth stimulation in vivo and furthermore that this limit may be lost altogether in fibroblasts associated with epithelial tumors.

Adenoma↗
PubMed1986

Estimation of the primordial pool size of the mouse liver using a histochemically demonstrable X-linked enzyme in the adult female mouse.

We have used a histochemical technique to study cellular mosaicism in the livers of female mice heterozygous for an abnormal form of the X-linked enzyme ornithine carbamoyltransferase. The proportion of cells expressing the normal enzyme was found to be consistent within a liver lobe, but discordant between lobes, with as few as 4% or as many as 91% of cells being enzyme positive. Systematic observation of variation of the proportion of positive cells in different lobes of 12 mice was used to calculate the primordial pool size for each lobe and for the liver as a whole. Although confidence limits for this small study are wide, the data suggest that the liver pool is about 15 cells, and that it enlarges to at least 50 cells before subdividing into six lobe pools ranging in size from a minimum of 4 to a maximum of at least 14 cells.

Animals↗
PubMed1985

Management of selected patients with hyperprolactinaemia by partial hypophysectomy.

Results are reported in 35 patients with prolactinomas who underwent pituitary surgery within the past five years. After surgery prolactin concentrations became normal in 26 patients and symptoms were alleviated, and nine normal pregnancies were achieved in seven women, including all those who had complained of infertility. Normal prolactin concentrations were restored in 16 of 17 patients with tumours 5-19 mm in diameter but in only six of 11 with tumours less than or equal to 4 mm and four of seven with tumours greater than or equal to 20 mm. Normal prolactin concentrations were restored in all those with preoperative concentrations below 1000 mU/l but in none of those with concentrations above 10 000 mU/l. Although not all of the patients were followed up for five years, hyperprolactinaemia did not recur in any patient whose prolactin concentration had returned to normal six weeks after surgery. This included 16 patients with macroprolactinomas (greater than 10 mm in diameter), who were followed up for from two to five years. These data contrast strikingly with those reported by others at similar stages of follow up and show clearly that partial hypophysectomy offers an acceptable alternative treatment for selected patients with prolactinomas.

Adenoma↗
PubMed1985

Mitotic response to wounding in goitrous and normal rat thyroid: implications for thyroid growth control.

Thyroid growth in the rat in response to a sustained elevation of serum thyrotropin (TSH) is limited by a progressive desensitization of the follicular cells to the mitogenic action of TSH which is not reversed by withdrawal of stimulation or by reduction of cell number. This study shows that, in thyroids which have reached a 'plateau' of growth, wounding induces a marked local follicular cell mitotic response which is equal in magnitude to that seen in control glands. This demonstrates that these cells, which are refractory to TSH, have not lost the capacity to divide. It is concluded that limitation of TSH-induced thyroid growth is not due to a non-specific loss of mitotic capacity resulting from severe hypothyroidism or goitrogen toxicity, or to an inherent limitation of the number of divisions which a follicular cell can undergo. The implications of these findings are discussed.

Animals↗
PubMed1985

New technique for showing the relation of tomographic myocardial perfusion images obtained with thallium-201 to the coronary arteries.

A new technique has been developed for presenting myocardial tomograms that allows the observer to perceive the shape of the thallium-201 distribution directly. The surface of the myocardium was found by applying an interactive thresholding technique to a set of conventional transverse slices. Computer graphics techniques were used to display a shaded image of that surface on a television screen, showing the three dimensional shape of the myocardial surface from any chosen aspect. A set of normal preserved coronary arteries was digitised, and using scaling and transformation techniques these arteries were mapped on to the myocardial tomograms and a shaded surface image produced with superimposed coronary arteries. This provided a familiar anatomical framework for locating perfusion defects. Its value in identifying various diseased vessels was confirmed by a comparison of the tomographic findings with the angiographic findings in five individual cases.

Adult↗
PubMed1985

In vitro evidence for an intracellular mechanism limiting the thyroid follicular cell growth response to thyrotropin.

The purpose of this study was to further investigate the mechanism that limits thyroid growth in the presence of a sustained elevation of serum TSH. An in vitro thyroid follicle culture was used, thyroid function and growth being assessed by 131I- organification and [3H]thymidine incorporation into DNA, respectively. Normal thyroid follicles incorporated [3H]thymidine in response to added TSH and also organified 131I-. Follicles taken from rats previously given goitrogen for 80 days, however, organified 131I- in response to added TSH but did not incorporate [3H]thymidine. These in vitro results parallel those obtained in in vivo studies despite the disruption of thyroid architecture. We conclude that the growth desensitization seen in vivo during sustained serum TSH elevation is mediated by an intracellular change in the follicular cell (either at the receptor or postreceptor level) rather than by a locally acting chalone.

Amitrole↗
PubMed1985

Thyroid carcinoma and thyroiditis in an endemic goitre region before and after iodine prophylaxis.

Iodine prophylaxis was introduced to the moderately severe goitre endemic area in Salta, Argentina, in 1963. All thyroidectomies from a 20 year period were reviewed, and 148 thyroid malignancies carefully studied. The period from 5 to 15 years after iodization was associated with a lower frequency of follicular carcinomas and a higher frequency of papillary carcinomas than the period before and up to 5 years after prophylaxis. Lymphoid infiltration in the non-tumorous thyroid was relatively infrequent before iodine prophylaxis: it was much higher in each of the post-prophylaxis periods. These results, in agreement with other studies, support the view that an increased iodine intake is associated with an increased incidence of papillary carcinoma of the thyroid and thyroiditis.

Adenocarcinoma↗
PubMed1985

Medullary carcinoma.

This paper constitutes a brief review of recent developments related to medullary carcinoma of the thyroid gland. The following topics are discussed: definition; pathologic variants; mixed medullary and follicular carcinoma; C cell hyperplasia; and the possible existence of C cell adenoma.

Adenocarcinoma↗
PubMed1985

Clonal origin of mouse liver cell tumors.

The clonal origin of tumors was studied in a large series of liver cell tumors in mice. Tumors were induced with phenobarbitone alone or following N-nitroso-diethylamine administration in female mice heterozygous for the sparse-fur strain. In this strain, a histochemical technique can be used in heterozygotes to differentiate clearly between liver cells expressing the histochemically positive normal or the histochemically negative abnormal form of the X-linked enzyme ornithine carbamoyl transferase. Three hundred twenty-seven liver tumors in heterozygous female Spf mice were studied: 157 (48%) were uniformly negative, and 160 (49%) were positive (some with partial enzyme loss). One hundred fifty-four liver tumors in normal mice were studied; all were positive, with a frequency of partial enzyme loss similar to that seen in the heterozygotes. Ten (3%) of the tumors in the heterozygotes contained some separate groups of positive and negative cells, but no tumor was made up exclusively of such groups. Even the smallest recognizable tumors were made up of single-phenotype cells, which suggested that a polyclonal origin followed at a later stage by clonal selection was unlikely. It is concluded that at least 97% of the tumors were of single-cell origin, and that convincing evidence of a polyclonal origin was completely lacking. It is also concluded that the histochemical demonstration of an X-linked enzyme in tumors induced in female animals heterozygous for an abnormal form of that enzyme provides an extremely useful technique for the study of the origins of neoplasia.

Animals↗
PubMed1984

Body elemental composition, with particular reference to total and exchangeable sodium and potassium and total chlorine, in untreated and treated primary hyperaldosteronism.

The whole body content of sodium, potassium, chlorine, calcium, phosphorus and nitrogen was measured by neutron activation analysis in 13 patients with untreated primary hyperaldosteronism (Conn's syndrome; aldosterone-secreting adenoma). Concurrently, exchangeable sodium and potassium were estimated by isotope dilution. Results were compared with values in the same patients during treatment with potassium-conserving diuretics and again after removal of the adenoma; and also with those in a series of 30 patients having untreated essential hypertension. Both total body and exchangeable sodium were high in Conn's syndrome before treatment and were reduced by spironolactone or amiloride and by subsequent surgery. There was no evidence of alteration in the proportion of non-exchangeable sodium in this disease, in contrast to earlier reports. Total body and exchangeable potassium were low in untreated Conn's syndrome and increased to normal after therapy: the proportion of non-exchangeable potassium was similar before and after treatment, and also similar to that in essential hypertension. Total body chlorine was increased before treatment in Conn's syndrome and returned to normal with therapy; body calcium, phosphorus and nitrogen were normal throughout.

Adult↗
PubMed1984

Quantitative analysis of rotating gamma camera thallium-201 scintigrams of myocardium.

Detection of defects in myocardial uptake of thallium-201 has been investigated by tomography with a rotating gamma camera. Twenty patients, 17 of whom had symptoms suggestive but not diagnostic of angina, and three with definite angina, underwent exercise ECG testing. Thallium-201 was injected at peak stress, followed by tomographic imaging with 180 degree data collection. A repeat study 4 h later showed the resting blood flow (redistribution) pattern. Transverse, coronal and sagittal sections were reconstructed and stress and redistribution studies compared. Quantitative comparison of T1-201 uptake in the stress and redistribution sections was investigated using profile analysis. These results were compared with a visual assessment. Tomographic images clearly showed defects in myocardial uptake and enabled scans to be classified definitely as normal, ischaemic or showing previous myocardial infarction. Results agreed with those from exercise ECG where ECG findings were definite, and gave a clear diagnosis in cases with equivocal ECG results. Significant differences were demonstrated between stress and resting uptake profiles for all segments judged ischaemic on stress from the images alone. A 'normal' profile was obtained to permit identification of infarcted regions. While quantitative analysis enabled the tomograms to be classified objectively, qualitative assessment was equally effective in nearly every case, possibly due to the clear and unconfusing image presentation.

Angina Pectoris↗
PubMed1984

Whole-body elemental composition in patients with renal failure and after transplantation studied using total-body neutron-activation analysis.

Whole body elemental composition in seventy-five patients with either renal failure or a kidney transplant was measured by neutron-activation analysis and whole-body counting. Comparison was made with expected normal values and with a control group; between undialysed, dialysed and transplanted patients; and between those receiving dialysis treatment for various periods. A frequent finding was low body calcium, reflecting the prevalence of renal osteodystrophy. Sodium and chlorine were increased in undialysed patients, a consequence of their renal disease. Patients with transplanted kidneys had reduced amounts of most elements, indicating decreased lean body mass, but increased body weight, probably due to excess fat.

Body Composition↗
PubMed1984

Glandular duodenal carcinoid--a somatostatin rich tumour with neuroendocrine associations.

The clinical and pathological features of four cases of duodenal carcinoid tumour are presented. All four tumours showed a glandular pattern, and in three cases this was associated with psammoma bodies. In three tumours somatostatin was identified by immunocytochemistry in most tumour cells. In two cases the duodenal tumours were associated with von Recklinghausen's disease and phaeochromocytoma. The importance of these unusual features is discussed, and it is suggested that these glandular carcinoids are a specific subgroup of endocrine cell tumours which appear to have potentially important clinical and pathological associations.

Adrenal Gland Neoplasms↗