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Biomedical subjects

E H Williams

Publications and source records attributed to E H Williams.

At least 37 records · Page 2Linked to original sources

A temporal and spatial study of the synthesis and degradation of water-soluble and insoluble proteins in galactosemic rat lenses.

Events of synthesis and degradation of water-soluble and -insoluble rat lens proteins were examined during a 21-day period of galactose-induced cataractogenesis. Epithelial cells continued to synthesize both fractions of proteins throughout the duration of the experiment. There were few qualitative changes in the pattern of proteins expressed and the rate of synthesis did not decrease. In contrast, synthesis of both water-soluble and -insoluble proteins by the cortical cells decreased and then became totally inhibited indicating no selective or differential inhibition of synthesis of one protein fraction, but that both water-soluble and -insoluble proteins in the cortical cells are equally affected by the metabolic changes associated with galactose-induced cataractogenesis. The cells within the nuclear region of control lenses were capable of incorporating [35S]-methionine into protein. This synthesis was completely abolished in 7- and 14-day nuclear cells. Labeled proteins were found to be present in the 21-day nuclear preparation to a level almost three times greater than that observed in the control nucleus. Degradation was minimal in both fractions of epithelial proteins, whereas selective degradation of proteins from both fractions was apparent in 14- and 21-day cortical cells. At day 14, the water-soluble protein profile from nuclear cells became less complex with the loss of several major bands, but these bands as well as some unique bands appeared at day 21. The profile of water-insoluble nuclear proteins remained unchanged over 21 days.

Animals↗

Effects of ketanserin on peripheral blood flow, haemorheology, and platelet function in patients with Raynaud's phenomenon.

Ketanserin, 40 mg b.i.d., or matching placebo were administered for 8 weeks each in a randomised double-blind crossover design to 23 patients with Raynaud's phenomenon. Ketanserin had no effect on Doppler arterial patency or blood flow at rest, 37 degrees C, 15 degrees C, or during recovery after cold challenge. Red cell deformability index and whole blood viscosity were not significantly affected by ketanserin treatment. In vivo bleeding time was prolonged on ketanserin (p less than 0.05) but beta-thromboglobulin and platelet factor 4 were unaffected. There was a nonsignificant decrease in platelet aggregation response to serotonin but no change at all with other aggregating agents on treatment with ketanserin.

Adult↗

Endemic Kaposi's sarcoma: incidence and risk factors in the West Nile District of Uganda.

Out of 72 Kaposi's sarcoma patients diagnosed between 1951 and March 1976 at Kuluva Hospital, West Nile District, Uganda, 64 with known co-ordinates were plotted on a map. Sixty-two of these were noted to live at an altitude of 853 metres or more (greater than or equal to 2,800 feet). Twenty-four patients were thought to be still alive and visits were made to their homes. Space-time grouping of four cases was noted on two occasions, although analysis did not reveal statistically significant clustering. A case-control study employing an interview questionnaire with 32 variables was performed on 19 patients and their age- and sex-matched neighbourhood controls, and sera were collected from both groups and from their families for estimation of viral antibody titres. The results demonstrated that cases tended to be post-pubertal males, a high proportion of whom had been bitten by a blood-sucking insect identified as being similar to Haematopota. Both cases and controls had raised antibody levels to cytomegalovirus, but cases obtained their drinking water more commonly from rivers whereas controls tended to use water from springs, boreholes or pipes.

Adolescent↗

Epstein-Barr virus markers in a series of Burkitt's lymphomas from the West Nile District, Uganda.

In an epidemiological survey in the West Nile District of Uganda, 70 pathologically confirmed BL cases were detected over a 5-yr period; this corresponded to an annual incidence rate of 1.6 per 100,000 general population or about 5 per 100,000 children in the age group 5-14 yr. Of the confirmed cases which were examined by EBV/DNA molecular hybridization, 96% were found to contain an average of 38 EBV genome equivalents per tumour cell, whereas none of the examined unconfirmed cases did. Duplicate hybridization assays in two laboratories were in close agreement. Serological testing showed that 91% of the confirmed BL cases had elevated EBV/VCA titres (greater than or equal to 160) and 64% were EA(D)-positive (greater than or equal to 10). Most of the cases with high EBV/genome content had high VCA titres, but there was a poor correlation between the two parameters among all cases. This study confirms that in high BL incidence areas the association between EBV and this lymphoma is almost constant, whereas it is exceptional in low-incidence areas. This further supports the aetiological implication of EBV in the endemicity of this tumor in equatorial Africa.

Adolescent↗

Periosteal transection for correction of angular limb deformities in foals.

Seventeen foals with angular limb deformities of the distal end of the radius (valgus: 26 limbs), distal end of the tibia (valgus: 6 limbs), and distal end of the 3rd metacarpal bone/metatarsal bone (varus: 4 limbs) were treated surgically by means of hemicircumferential division of the periosteum proximal to the involved growth plate, at the concave side of the bone. There was some correction in all cases. The best results were seen in the radius, where 22 of 25 limbs were corrected to a deviation of 4 degrees or less. Satisfactory correction was obtained in the 6 tibias, the 2 third metacarpal bones, and the 2 metatarsal bones.

Animals↗

Final case reporting from the Ugandan prospective study of the relationship between EBV and Burkitt's lymphoma.

A prospective epidemiological study was carried out in the West Nile District of Uganda from 1972 to 1979 in order to investigate the aetiological role of the Epstein-Barr virus (EBV) in Burkitt's lymphoma (BL). By 1976, fourteen BL cases had been detected among the 42,000 children originally bled in the study area. Testing of sera from BL candidates and neighbourhood controls showed that children who develop BL later have EBV/VCA titres several dilutions higher than their age- and sex-matched neighbours. This appearance of a strong EBV activity long before BL development was taken as evidence of a causal role of EBV in BL. In order to add to the unique material of pre-bled BL cases, BL detection was continued up to March 1979 when field work became impossible in Uganda. Two additional pre-bled BL cases were found during this extension of the study. The serological and virological evaluation of these additional cases showed that the EBV/VCA titres, but not the EA and EBNA titres, were about two dilutions higher in the BL candidates than in the controls. Hybridization assays showed that both lymphomas contained EBV/DNA in the tumour cells. These additional results thus confirm the findings in the first 14 cases and strengthen the epidemiological evidence for a causal role of the EBV in endemic BL.

Antibodies, Viral↗

Anterior spinal artery syndrome with chronic traumatic aortic aneurysm.

Shortly after severe blunt chest trauma, a young man experienced neurological symptoms suggestive of a spinal cord lesion at the lower thoracic level. The symptoms resolved at first, but then recurred 3 years later and progressed slowly. Neurological workup failed to define the cause until a thoracic aortogram showed an aneurysm in the middle portion of the descending aorta in close proximity to a vessel supplying the anterior spinal artery. After the operative repair with precautions taken to avoid further neurological injury, the neurologic deficit resolved partially. Because of the potential for symptomatic spinal cord ischemia resulting from lesions of the aorta, angiographic delineation of the spinal cord blood supply is valuable in planning operative repair.

Adult↗

Effect of temperature during potassium arrest on myocardial metabolism and function.

Past studies have not established the optimal myocardial temperature range for hyperkalemic arrest but have generated controversy regarding the safety of exposing the myocardium to more profound levels of hypothermia. We therefore used the isolated working rat heart model of ischemic arrest to study the metabolic and functional effects of cardioplegia at the full range of temperatures pertinent clinically. Experimental conditions were designed to reliably control and maintain myocardial temperature during the 60 minute arrest period. We found that nearly full recovery of function occurred when hearts were arrested at or below 16 degrees C. High-energy phosphate levels measured immediately after arrest were better maintained at 4 degrees and 8 degrees C, despite evidence of decreased anaerobic glycolysis. When measured after the recovery period, high-energy phosphate levels returned to somewhat less than control levels in all groups arrested at or below 24 degrees C. Myocardial glucose utilization was best preserved in hearts arrested at or below 12 degrees C. We found no evidence that greater myocardial edema resulted from arrest at colder temperatures. Severe and permanent damage was observed when hearts were arrested at or above 28 degrees C. In this model, therefore, the best overall metabolic and functional protection occurred when hearts were maintained at 12 degrees C or below potassium-induced cardioplegia. Our results support the idea that cold injury to the heart does not occur and that colder temperatures provide better protection from ischemic myocardial injury.

Adenosine Triphosphate↗

Electrical coupling among heart cells in the absence of ultrastructurally defined gap junctions.

Cells from the ventricles of 7-day chick embryos were aggregated into spheroidal clusters by 48 hr of culture on a gyratory platform. All aggregates beat spontaneously and rhythmically. Microelectrode impalement of widely separated cells within aggregates indicated that they were coupled, as evidenced by a mean coupling ratio (delta V2/ delta V1) of 0.81 +/- 0.09, and by simultaneity of intrinsic electrical activity (action potentials and subthreshold voltage fluctuation). In freeze-fracture preparations, the cell surfaces contained numerous small groups of intramembrane protein (IMP) particles, arranged in macular clusters, and linear and circular arrays. Using the criterion of 4 clustered IMP particles to defined a minimal gap junction, 0.27% of the total P-face examined was devoted to gap junctional area. Within such clusters particles were packed at about 8200/micrometer2; in nonjunctional regions, particles were scattered at a density of about 2000/micrometer2. When exposed to cycloheximide (CHX: 50 micrograms/ml) for 24--48 hr, coupling ratio declined to 0.44. This decrease could be attributed largely to leakiness of the nonjunctional membrane. Aggregates continued to beat rhythmically and in a coordinated fashion even after 72 hr in inhibitor. However, between 3--21 hr in CHX gap junctional area declined to 0.10%, and all particle clusters disappeared from the P-faces of aggregates in CHX for 24 or 48 hr. Neither macular nor linear particle arrays were seen. We conclude that organized gap junctions are unnecessary for electrotonic coupling between embryonic heart cells. These findings support the idea that low-resistance cell-to-cell pathways may exist as isolated channels scattered throughout the area of closely apposed plasma membranes.

Action Potentials↗

Use of cold cardioplegic solution for vein graft distention and preservation: a light and scanning electron microscopic study.

To evaluate the effect of a cardioplegic solution on the endothelium of the saphenous vein, portions of this vein were harvested from each of 5 patients undergoing coronary artery bypass operation. Each sample was divided into five segments. One segment was distended with heparinized saline solution, one with heparinized blood, and one with heparinized cardioplegic solution (25 mEq of potassium per liter). All of the distending solutions were kept at 10 degrees C, and pressure was carefully limited to 200 mm Hg. The fourth segment of vein was distended with heparinized saline solution but no effort was made to limit distending pressure, and the fifth segment was not distended. All samples were then examined with light and scanning electron microscopy. There were no great morphological differences in the endothelium of veins distended to 200 mm Hg with saline solution, blood, or cardioplegic solution. The morphology of these samples compared favorably with the control vein endothelium although scattered areas of endothelial disruption were present in every sample. Veins distended without pressure control showed massive endothelial disruption. The particular solution used to distend the sephenous veins is not as important as limiting the distending pressure.

Blood↗

Protein degradation and synthesis during recovery from myocardial ischemia.

Rates of synthesis and degradation of heart protein were measured during 30 or 60 min of myocardial ischemia and during the 30 or 60 min following these ischemic periods. During ischemia, rates of protein synthesis and degradation were reduced. Resumption of control rates of coronary flow after 30 min of ischemia resulted in complete restoration of creatine phosphate and partial recovery of ATP (75%), developed pressure (79%), and cardiac output (80%). After 60 min of ischemia, restoration of flow completely restored creatine phosphate but resulted in poor recovery of ATP (57%), developed pressure (26%), and cardiac output (63%). During the recovery phase, rates of protein synthesis and degradation of protein to free amino acids were the same as in hearts that had been perfused for a comparable period as working aerobic preparations. These findings were consistent with inhibition of an initial step in proteolysis during the period of ischemia followed by return to control rates of degradation when oxygen delivery and energy levels were restored.

Adenosine Triphosphate↗