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Biomedical subjects

D Ellis

Publications and source records attributed to D Ellis.

At least 199 records · Page 11Linked to original sources
PubMed1984

3'-Acetyl-3,5-diiodo-L-thyronine: a novel highly active thyromimetic with low receptor affinity.

The 4'-phenolic hydroxyl group of thyroid hormones plays an important role in receptor binding, and it has been suggested that the interaction of this hydroxyl group with the receptor involves hydrogen bonding via donation of the acidic hydrogen in a trans disposition to the 3'-substituent of the hormones. In order to test this hypothesis we have synthesised, and measured the hepatic receptor affinity and thyromimetic activity of 3'-acetyl-3,5-diiodo-L-thyronine (3'-Ac-T2), a compound in which the formation of such a receptor-phenol hydrogen bond is precluded by the presence of a strong intramolecular hydrogen bond between the 3'-acetyl- and 4'-hydroxyl groups. In confirmation of the hypothesis, 3'-Ac-T2 has a low affinity (0.5% of that of 3,5,3'-triiodo-L-thyronine, T3) for the T3-receptor in isolated rat hepatic nuclei. By contrast the thyromimetic activity (assessed by its ability to induce rat hepatic glycerol-3-phosphate dehydrogenase and increase the qO2 of liver slices) was roughly equal to that of T3. This apparent discrepancy was resolved when it was found that the capacity of 3'-Ac-T2 to occupy hepatic receptors after in vivo administration, was about 100 times greater than predicted from its in vitro affinity. The reason for this difference between in vivo and in vitro nuclear binding is unknown at the present time.

Animals↗
PubMed1984

Mycotic aneurysm of the small bowel presenting as gastrointestinal haemorrhage.

Since the advent of modern antibiotic therapy and active surgical treatment of bacterial endocarditis, septic embolization of the systemic circulation is rarely seen. An unusual presentation of a mycotic aneurysm with gastrointestinal haemorrhage in a patient with non-Hodgkin's lymphoma and aortic valvular endocarditis which had been managed by aortic valve replacement six weeks before the haemorrhage occurred is reported.

Aged↗
PubMed1984

A new model of glucocorticoid-induced metanephric maldevelopment.

A new experimental model of glucocorticoid-induced tubular cyst formation has been developed in metanephric organ culture. The addition of cortisol (1.4 X 10(-5) M) to chemically defined serum-free culture medium produces cystic changes during in vitro nephrogenesis . The model isolates the role of glucocorticoids in experimental cyst formation.

Animals↗
PubMed1984

Altering hydrodynamic variables influences PGI2 production by isolated lungs and endothelial cells.

Because deformation of lung tissue stimulates prostaglandin synthesis, we wanted to investigate whether hydrodynamic forces would affect lung prostacyclin (PGI2) production. To test the hypothesis that lung prostacyclin synthesis was flow dependent, we examined lung prostacyclin production after flow alterations. Using a salt solution that contained either Ficoll or albumin as a perfusate, we changed the flow to half and to double the control flow. When flow was changed, lung prostacyclin production followed changes in flow and pressure drop. When flow was varied in lungs treated with indomethacin, prostacyclin production was too low to be measurable. Variations in pressure pulsatility at constant mean flow had no influence on lung prostacyclin production. Since vascular distension may also stimulate prostacyclin production, we increased venous pressure. An increase in venous pressure (from 2.1 to 4.8 mmHg) had no effect on prostacyclin production; a further increase in venous pressure (to 7.5 mmHg) initiated edema and caused a large increase in prostacyclin production. When we subjected monolayers of endothelial cells cultured in wells to defined shear rates, the prostacyclin concentration in the supernatant quickly increased to a maximum. The absence of further increase with greater shear may have reflected feedback control of prostacyclin synthesis. The results indicated that hydrodynamic disturbances affect endothelial cells and stimulate arachidonate metabolism. Lung prostacyclin production may be related to flow. However, this effect is small compared with the lung prostacyclin production during edema formation.

Animals↗
PubMed1984

Canadian American ticlopidine study (cats) in thromboembolic stroke.

Approximately 1000 patients who have suffered a well-documented thromboembolic stroke within two weeks to four months of study entry will be enrolled in this double-blind, randomized, placebo controlled, parallel group trial. Five Canadian and five United States study centers will participate. The enrollment period will be two and one half years, and follow-up will run for an additional six months to a common termination point at three years. Ticlopidine hydrochloride, administered as two 125 mg tablets b.i.d. (500 mg/day total dose) will be compared with placebo for efficacy in the prevention of recurrent stroke, myocardial infarction, cardiovascular death, and overall mortality. Inclusion and exclusion criteria will be the minimum necessary to provide safety and scientific validity. After a screening visit, qualifying patients will be randomly assigned to ticlopidine or placebo. Follow-up laboratory studies for monitoring complete blood and platelet counts will be made at weeks 2, 4, 6, 8, 10 and 12, and then months 4, 5, 6, 8 and then every 4 months thereafter. Follow-up clinic visits will be made at 1 month, 4 months, and then every four months thereafter for clinical evaluation and for dispensing test medication. Study outcome events will be appropriately documented on case report forms. The statistical analysis will evaluate the initial comparability of the two treatment groups, and the principal outcomes of the two groups will be compared by using the Mantel-Haenszel life table analysis.

Anticoagulants↗
PubMed1984

The chemotherapy of rodent malaria XXXVI. Part IV. The activity of a new 8-aminoquinoline, WR 225,448 against exo-erythrocytic schizonts of Plasmodium yoelii yoelii.

Light microscope and ultrastructural studies show that WR 225,448, an 8-aminoquinoline related to primaquine, causes substantial damage to developing pre-erythrocytic (EE) schizonts of Plasmodium yoelii yoelii in the liver of young rats. In addition to lesions of the mitochondria and nuclear membranes, secretory granules in the parasite fail to reach the surrounding host cell cytoplasm across the parasite membrane. The effective dose of WR 225,448 is much lower than that of primaquine. However, hepatic damage is also seen in treated animals. This may be the summation of damage produced by the experimental inoculation of a large quantity of infective salivary gland tissue from mosquitoes (which is also seen in untreated animals) plus toxic effects of the drug itself. Particular attention would have to be directed to this aspect in preclinical toxicity testing of the compound.

Aminoquinolines↗
PubMed1984

Hydrocortisone-induced cystic metanephric maldevelopment in serum-free organ culture.

To investigate the basic pathophysiology of renal cystic maldevelopment, the production of renal cysts was studied in a newly developed murine metanephric organ culture system. In this isolated, nonvascularized system, the addition of hydrocortisone (1.4 X 10(-5) M) to completely characterized, serum-free growth medium produced striking tubular cystic abnormalities. As nephron obstruction did not occur in the nonperfused organ culture system in which neither glomerular filtration nor urine flow were present, the model experimentally isolated the roles of tubular cell metabolism and tubular wall extracellular matrix development in the production of cystic alterations. Analysis with the techniques of intact nephron microdissection and light and electron microscopy demonstrated that organ culture cysts developed in proximal tubules amid a normal background of organotypic tubular differentiation and glomerular epithelial development. Frank cystic development in the system was regularly preceded by ultrastructural alterations in and around the walls of differentiating proximal tubules. Such changes consisted of basolateral intercellular spreading which increased with progressive tubular dilation and irregular thickening and lamellation of tubular basal laminae. The ultrastructural features of the model suggest roles for hydrocortisone-induced alterations in both tubular transport processes and basal lamina structure in the experimental production of cysts. We conclude that the production of cystic changes in organ culture by hydrocortisone permits highly controlled study of the roles of altered tubular cell and basal lamina metabolism in the pathogenesis of cystic metanephric maldevelopment.

Animals↗
PubMed1983

Cyst formation in metanephric organ culture induced by cis-dichlorodiammineplatinum (II).

A new experimental model of renal tubular cyst formation has been developed in metanephric organ culture. The addition of cis-dichlorodiammineplatinum (II), 50 micrograms/ml, to culture medium induces cystic changes during in vitro nephrogenesis. The model has particular utility in the study of basic mechanisms underlying renal tubular cystic changes, as well as the mechanisms by which nephrotoxins may mediate renal tubular injury.

Animals↗
PubMed1983

Proteinuria in children with insulin-dependent diabetes: relationship to duration of disease, metabolic control, and retinal changes.

The relationship of early retinal changes and subclinical proteinuria to duration and metabolic regulation of insulin-dependent diabetes was studied in 67 children. Retinopathy was found in 25 patients and occurred almost exclusively (96%) in those with duration of disease longer than five years. Glomerular filtration rate was normal or increased in all patients. Urinary excretion of beta 2-microglobulin, albumin, transferrin, and IgG was significantly increased in patients, as compared with controls, whereas serum concentrations of these proteins were generally normal. The mechanisms responsible for the hyperexcretion of both large and small proteins are unclear but probably involve both glomerular and tubular dysfunction. Increased urinary protein excretion occurred independently of duration of disease. Retinopathy but not microproteinuria was more common in patients with glycosylated hemoglobin greater than 11% and in those with duration of disease longer than five years. Although a significant association was found between retinopathy and the hyperexcretion of one or more of the large molecular weight proteins, the weight of the evidence suggests that these two sequelae of diabetes differ in their pathogenesis. Long-term follow-up of these patients may provide insight as to their risk of developing more serious retinopathy or nephropathy, and whether good glycemic control may protect against these complications of insulin-dependent diabetes.

Adolescent↗
PubMed1983

Diabetic nephropathy in adolescence: appearance during improved glycemic control.

Two girls, aged 15 and 14 years, with poorly controlled insulin-dependent diabetes (IDD) of 9 and 7 years duration, respectively, developed overt and persistent proteinuria shortly after rapid increases in insulin therapy and improved glycemic control. Renal biopsies showed diffuse diabetic glomerulosclerosis. Both patients maintained normal or increased creatinine clearances. Direct ophthalmoscopy and fluorescein retinal angiography demonstrated nonproliferative diabetic retinopathy in the first patient, which deteriorated after 6 weeks of strict metabolic control; the second patient had normal retinas. The appearance of clinical proteinuria during this brief period of good glycemic control suggests that the latter may have unmasked a preexisting condition. Possible pathophysiologic mechanisms initiating the proteinuria in these patients are reviewed.

Adolescent↗
PubMed1983

Urinary immune complexes in patients with glomerular diseases. Their possible diagnostic implications.

Urine specimens from 65 patients with glomerular disease and from 62 controls were tested for the presence of immune complexes by agarose gel zone electrophoresis. Urinary immune complexes (UICs) were found in 18% of patients, correlating with the simultaneous occurrence of serum immune complexes and depending differentially on the histologic form of glomerular disorder. The UICs were found preponderantly in patients with severe crescentic glomerulonephritis, who had "gaps" in the glomerular basement membrane; in patients with epimembranous electron-dense deposits; and in patients with membrano-proliferative glomerulonephritis. The UICs were detected in no patients with focal glomerular sclerosis or mesangial proliferative glomerulonephritis and in only one of 23 patients with minimal-change disease. None of 62 controls had UICs. Passage of immune complexes through filtering structures of the kidneys may be a consequence of their focal or diffuse damage. Detection of UICs may provide a noninvasive means of assessing the extent of tissue injury in patients with glomerular disorders.

Antigen-Antibody Complex↗
PubMed1983

Development of renal basement membrane glycoproteins in metanephric organ culture.

Because of the importance of renal basement membrane glycoproteins in normal and abnormal tubular and glomerular morphogenesis, structure, and function, the sequential development of fibronectin, GP-2, and entactin was studied in vivo and in a newly developed, serum-free mouse metanephric organ culture system. The organ culture system permits advanced tubular differentiation and glomerular epithelial development of whole metanephros without perfusion or urine formation. Affinity-purified antibodies and immunohistologic techniques were used, and the ontogeny of basement membrane glycoproteins was characterized in vivo and in vitro. It was thus possible to characterize the pattern of normal renal basement membrane glycoprotein production and to comparatively study renal glomerular and tubular basement membrane formation in the presence and the absence of endothelial and/or mesangial influences. Both in vivo and in vitro undifferentiated mesenchyme expressed fibronectin but not GP-2 or entactin. Further, both in vivo and in vitro, all three glycoproteins developed in the basement membranes of the earliest recognizable tubular and glomerular forms. Because of the sharp parallel between in vivo and in vitro basement membrane glycoprotein production we conclude that the whole organ metanephric culture system is a useful model for the study of renal basement membrane development. Further, based on the pattern of in vitro basement membrane production, it may be concluded that tubular and glomerular epithelial cells are capable of producing basement membrane glycoproteins in the absence of endothelial or recognizable mesangial cells following initial embryonic induction.

Animals↗