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Biomedical subjects

D H Adams

Publications and source records attributed to D H Adams.

At least 217 records · Page 12Linked to original sources

Further studies on the size and composition of the chick embryo fibroblast cytosolic DNA complex.

The chick embryo fibroblast cytosolic DNA complex shows anomalous elution behaviour on agarose gel column chromatography. The indicated molecular size varies between 5 X 10(5) dalton (higher exclusion limit gels) and 1.4 X 10(6) dalton (lower exclusion limit gels). Chromatography on lower exclusion limit gels shows the [3H]thymidine labelled (DNA) complex as a sharp peak, coincident with a peak of [3H]uridine and [3H]lysine labelling and similar pulse labelling patterns for the three precursors but with DNA labelling lagging behind RNA and protein. Both cultured and uncultured cell cytosols show an A260 peak coincident with the [3H]precursor labelling peaks.

Animals↗

The nature of the scrapie agent.

There now seems little doubt that the infective agent of scrapie cannot be accommodated within current concepts of virology/molecular biology. It is proposed: that the basic infective entity is a nucleic acid fragment (oligonucleotide) of some 40 bp coupled with specific (but host encoded) protein totalling approximately 10(5) daltons, a significant proportion of which is in the form of proteolipid; that the nucleic acid fragment reprograms the host cell on the chemically switched microprocessor network analogy already proposed; that the nucleic acid fragment has no initiation sequence for replication: it is therefore non-infective; that the nucleic acid fragment can replicate when associated with the specific protein component because the resulting complex is able to displace mobile genetic element flanking sequences (similar to the yeast delta sequence). The function of the protein is to provide a scaffolding which allows the nucleic acid fragment to be assimilated into the replication cycle of the mobile genetic element as a whole.

Animals↗

Disseminated intravascular coagulation caused by abdominal aortic aneurysm.

Disseminated intravascular coagulation (DIC) has been described as an occasional complication of abdominal aortic aneurysm. This is usually a perioperative coagulopathy, which may progress into a hemorrhagic diathesis. Rarely, DIC is present preoperatively as a result of the aneurysm itself. In the presence of additional pathophysiologic factors, a "compensated state" of secondary fibrinolysis may deteriorate into a clinically manifest coagulopathy. Heparin can be a useful adjunct in preoperative management of DIC, but definitive treatment requires surgical repair of the aneurysm. Long-term follow-up is essential to ensure that DIC is due to the aneurysm and that other disease processes are not overlooked. We report a case of DIC caused by an abdominal aortic aneurysm, with resolution after surgical treatment.

Aged↗

Studies on the cytosolic DNA of chick embryo fibroblasts and its uptake by recipient cultured cells.

Cytosol and extruded DNA complexes from cultured chick embryo fibroblast cells have been separated by agarose gel chromatography at intervals after pulse labelling with [3H]thymidine. The proportion of the various cytosol components changed markedly with time: there was a lag period of 3 hr before the major labelled (5 X 10(5) dalton) DNA complex appeared in the cytosol, and a further lag period of 5 hr before it was extruded from the cell. Cultured chick embryo fibroblast, and rat spleen, cells rapidly and very efficiently import their own or each others cytosolic DNA complexes into their respective cytosol fractions: the material recovered from the cytosol of recipient cells is characteristic of the presented material. Homologous cytosolic DNA complex presented to chick embryo fibroblast cells also becomes associated with the nucleus. The rat at which this occurs is comparable with the rate of incorporation of [3H]thymidine into nuclear DNA.

Animals↗

Further studies on the extrusion of cytosol macromolecules by cultured chick embryo fibroblast cells.

The RNA and lipid-associated macromolecules extruded by chick embryo fibroblast cells have been analysed by chromatography. The results taken with those previously obtained suggest that cultured chick embryo fibroblasts excrete a wide range of cytosol macromolecules into the surrounding medium. As previously found with DNA and protein, the chromatographic patterns found with supernatant and cell cytosol preparations were closely similar, suggesting that the media supernatant macromolecules are cytosal derived. A proportion of the RNA and lipid associated material elutes at the same position as the previously observed for DNA and protein on gel exclusion chromatography, suggesting that cell cytosol contains a discrete DNA-RNA-protein lipid complex (size approx 5 X 10(5) dalton) which is extruded by cultured cells.

Animals↗

Oral cefuroxime axetil: clinical pharmacology and comparative dose studies in urinary tract infection.

Cefuroxime axetil, an orally absorbed pro-drug of cefuroxime was used to treat a mainly elderly group of patients with symptomatic urinary tract infections. The drug was clinically effective and the bacteriological short term and long term cure rates (55% and 48% respectively) comparable to those of other antibiotics. The study had to be terminated however after the development of three cases of antibiotic associated colitis. Studies of the pharmacokinetics of the drug in volunteers gave inconsistent results suggesting that there may be variable bioavailability of the compound.

Administration, Oral↗

The cytosol origin of macromolecules extruded by cultured chick embryo fibroblast cells.

The DNA and protein extruded by chick embryo fibroblast cells has been analysed by chromatography. A high proportion of the DNA is in the form of a protein-complex of size around 5 X 10(5) dalton. The patterns of the DNA and protein extruded into the supernatant are closely similar in many respects to those found in the cell cytosol. It is concluded that the macromolecular material extruded by cells in culture is of cytosol origin: a possible function in terms of "information" carriage is proposed.

Animals↗

Pneumopericardium resulting in cardiac tamponade.

Cardiac tamponade most commonly results from accumulation of blood or other fluids within the pericardial sac. However, there is a growing body of clinical evidence showing that pneumopericardium can lead to cardiac tamponade in a large number of patients. Including those in the present report, a total of 252 patients with pneumopericardium are available for review. Interestingly, cardiac tamponade developed in 94 patients, or 37% of this group, because of air within the pericardial space. Pneumopericardium resulting in tamponade most frequently occurs in trauma patients or in newborn infants requiring positive pressure ventilation. This syndrome can be recognized promptly because of its characteristic physical findings and radiographic features. Although air tamponade can be treated effectively by either needle aspiration or insertion of a pericardial tube, the development of a pneumopericardium is a bad prognostic sign. Out of the 221 patients reported in the literature whose outcome is known, 127 (57%) died. In the group with a tension pneumopericardium, the mortality was 56% (53 out of 94 patients). Even without the development of tension, however, pneumopericardium was associated with a 58% mortality (74 out of 127 patients) due to other underlying disease processes.

Adult↗

The DNA extruded by rat spleen cells in culture.

1. Part of the DNA extruded by cultured rat spleen cells occurs in the form of a low density lipid complex. 2. The present work indicates that this complex is also associated with protein but not with RNA and its elementary properties have been studied. 3. For example, it is destroyed by freezing and thawing or by deoxycholate treatment and small quantities of copper salts added to the medium may either inhibit or stimulate its release depending on the conditions.

Animals↗

The natural history and recommended management of patients with traumatic coronary artery fistulas.

Traumatic coronary artery fistulas are reported less often than other complications resulting from both penetrating and blunt trauma to the heart. We describe a 50-year-old man in whom the natural history of a traumatic coronary fistula is well documented. This patient, who was referred for evaluation and treatment of complications of a traumatic coronary artery fistula resulting from a shrapnel injury 31 years before admission to the hospital, had five cardiac catheterizations prior to undergoing definitive surgical repair. During this period, he progressed from being totally asymptomatic to having disabling angina and congestive heart failure. These symptoms developed even though the patient's left-to-right shunt remained constant; moreover, the symptoms appeared to develop secondary to a "steal" of myocardial blood flow from the uninvolved coronary arterial bed through tortuous collaterals. Based on this experience and supported by published reports of 25 other patients, we recommend that nearly all patients with traumatic coronary artery fistulas be considered as candidates for elective surgical repair in order to prevent the eventual development of serious and possibly life-threatening complications. Operative repair can be accomplished safely with excellent long-term results.

Angina Pectoris↗

Evidence that ischemic cell death begins in the subendocardium independent of variations in collateral flow or wall tension.

Irreversible ischemic injury occurs after coronary artery occlusion in vivo, first in the subendocardium and progressing toward the subepicardium over time, presumably due to transmural variations in collateral flow or wall tension. In this study, 10 left ventricular globally ischemic slabs were created that were free of wall tension and collateral flow. The onset and completion of ischemic contracture were identified by means of a new tissue compressibility gauge designed for these studies. Transmural samples were obtained at 15 min intervals for determination of high-energy nucleotide levels and for ultrastructural analysis. The results show that there is a statistically significant gradient of ATP depletion, with the subendocardium consistently showing accelerated energy utilization compared with the subepicardium (p less than .05). Ultrastructural evidence of irreversible injury first appeared in the subendocardium at the onset of ischemic contracture and occurred when ATP levels declined to less than 1 mumol/g wet weight. In summary, these data show that during total ischemia in vitro, cell death begins in the subendocardium at the onset of ischemic contracture and progresses toward the subepicardium over time. These changes occurred independent of variations in collateral flow or wall tension. The results suggest that the increased risk of the subendocardium to ischemic injury previously noted in vivo may occur not only because of variations in collateral flow and wall tension, but may also be secondary to an increased metabolic rate of the subendocardium resulting in faster ATP use during the period of ischemia.

Adenosine Diphosphate↗

Stimulated and non-stimulated rat spleen cells release different DNA-complexes.

Isolated rat spleen cells released into the culture medium a complex containing newly-synthetized DNA. Upward sucrose density gradient centrifugation yielded material from non-stimulated cells at a major peak of density 1.03, with minor peaks at 1.04 and 1.055. However, the complex from cells stimulated with phytohaemagglutinin showed a major peak at 1.052, with little material at 1.03. The low densities indicated that the complexes contained a high proportion of lipid, confirmed by the incorporation of 3H-ethanolamine. Data indicate that newly synthesized DNA leaves the nucleus, crosses the cytoplasm, and associates with the cell membrane prior to leaving the cell as a complex with the DNA protected against nuclease activity.

Animals↗

Chemotherapy of herpes simplex virus encephalitis in mice by direct intracerebral injection.

The effects of 9-beta-D-arabinofuranosyladenine-5'-phosphate (ara-A-5'-P) on herpes simplex virus encephalitis in mice were studied. This drug is a monophosphate derivative of adenine arabinoside (ara-A). When administered by the intracerebral (ic) route, ara-A-5'-P was highly effective in virus-infected mice in the 17-20 g weight range provided therapy was begun before clinical symptoms of encephalitis appeared. The most effective dose schedule was found to be three daily ic injections totaling 400 micrograms/day (20 mg/kg) beginning on the third day after injection. Such treatment resulted in a survival rate of 50%-75% among infected mice after six months. In the early stages of many experiments, 90%-100% of the controls died whereas all of the treated animals survived.

Animals↗

Liposome toxicity in the mouse central nervous system.

This study has shown that while some liposomes are highly toxic to the central nervous system, others, of different composition, are tolerated well in the dosage used (0.02-0.05 ml = 4-12 mg of lipid/inoculum). Those composed of lecithin-cholesterol-dicetyl phosphate or lecithin-cholesterol-stearylamine produced generalised epileptic seizures and some deaths due to respiratory failure immediately after injection,and a subsequent widespread tissue necrosis. However liposomes composed of lecithin-cholesterol-phosphatidic acid, or dipalmitoyl lecithin only, produced minimal morphological changes and by the sixth day post-injection the pathology was limited to the mechanical trauma caused by the injection. It is concluded that liposomes of appropriate composition may be sufficiently benign to use as carriers of therapeutic agents into the CNS.

Amines↗