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Biomedical subjects

C Rees

Publications and source records attributed to C Rees.

At least 19 recordsLinked to original sources

Cooperative binding of the globular domains of histones H1 and H5 to DNA.

In view of the likely role of H1-H1 interactions in the stabilization of chromatin higher order structure, we have asked whether interactions can occur between the globular domains of the histone molecules. We have studied the properties of the isolated globular domains of H1 and the variant H5 (GH1 and GH5) and we have shown (by sedimentation analysis, electron microscopy, chemical cross-linking and nucleoprotein gel electrophoresis) that although GH1 shows no, and GH5 little if any, tendency to self-associate in dilute solution, they bind highly cooperatively to DNA. The resulting complexes appear to contain essentially continuous arrays of globular domains bridging 'tramlines' of DNA, similar to those formed with intact H1, presumably reflecting the ability of the globular domain to bind more than one DNA segment, as it is likely to do in the nucleosome. Additional (thicker) complexes are also formed with GH5, probably resulting from association of the primary complexes, possibly with binding of additional GH5. The highly cooperative nature of the binding, in close apposition, of GH1 and GH5 to DNA is fully compatible with the involvement of interactions between the globular domains of H1 and its variants in chromatin folding.

Animals

Facilitating project feedback: the use of poster presentations.

This article describes the use of student poster presentations as a means of feeding back to the whole group the results of project work. A technique usually associated with conferences, this format has been successfully used here to provide stimulation and creativity amongst one group of post-registration course members. It is suggested that not only could his approach be used by others, but that it has also the potential to be developed and applied in a variety of situations.

Audiovisual Aids

Septic pulmonary arteriovenous fistula. An unusual conduit for systemic embolization in right-sided valvular endocarditis.

Right-sided valvular (tricuspid, pulmonic) endocarditis is frequently complicated by septic pulmonary embolization. Systemic embolization may also rarely occur due to associated left-sided endocarditis or right-to-left shunting in patients with septal defects. This report documents the occurrence of systemic embolization causing a cerebrovascular accident in an intravenous drug abuser with recurrent tricuspid valve endocarditis due to an isolated peripheral septic pulmonary arteriovenous fistula. Noninvasive diagnosis of the fistula by cardiac auscultation, contrast echocardiography, and nuclear magnetic resonance imaging was confirmed by selective pulmonary angiography. Subselective balloon embolization of the pulmonary arteries feeding this fistula was accomplished.

Adult

Neurotoxicology dose/response assessment for several cholinesterase inhibitors: use of uncertainty factors.

Dose/response assessment for non-carcinogenic endpoints typically uses the Acceptable Daily Intake (ADI) or Reference Dose (RfD) approach, in which a dose believed to cause no toxic effect is divided by a number of safety or uncertainty factors (e.g., to control for variability and cross-species extrapolation), in order to estimate a dose presumed to have no adverse effects in humans. With the establishment of neurotoxicology testing guidelines, routine use of uncertainty factors to undertake neurotoxicity dose/response assessment procedures is likely. This approach to dose/response assessment has not yet been widely applied to neurotoxicity data. The purpose of this study was to assess the use of uncertainty factors and the assumptions underlying the use of the uncertainty factor method in assessing risk for several known human neurotoxicants. Because of the availability of a large neurotoxicity data base which included human exposure data, parathion, diisopropylfluorophosphate, physostigmine and acrylamide were chosen for this analysis. Literature searches were conducted for both human and animal data. The resulting data were assigned to one of five end point categories: Neurochemistry/neuropathology, physiology/consummatory behavior, sensory/motor, electrophysiology, and learning/memory behavior. No-observed-adverse-effect levels (NOAELs) and/or lowest-observed-adverse-effect levels (LOAELs) were determined when possible for each end point and for several species. Reference doses (RfDs) were calculated and compared across species. A number of issues and critical assumptions were identified.

Animals

Road to recovery.

The role of the nurse in giving information to patients has grown considerably following the work of researchers such as Hayward (1975), Boore (1978) and Wilson-Barnett (1978). From admission to discharge the nurse has a valuable educational role to play in helping patients come to terms with their present position and preparing them for the future. The questions facing nursing now are not whether nurses should undertake this role, but how well do they provide information? Do patients act on advice? And how far should relatives be included in the process of patient education? These are the questions that prompted the present study, in which 43 people completed questionnaires 6 to 8 weeks following discharge from hospital after cardiac surgery. Eighty-two per cent were completely or 'on the whole' satisfied with the information given, though the perceived adequacy varied between topics; 70% reported some associated behaviour change and in each case their relatives had been involved in receiving pre-discharge advice.

Aged

Normal and stenotic renal arteries: experimental balloon-expandable intraluminal stenting.

Elastic recoil of the vessel wall is a common cause of failure of percutaneous transluminal angioplasty in renal arteries. To oppose such recoil, balloon-expandable metal stents were implanted in artificially stenotic renal arteries in pigs and normal renal arteries in dogs and pigs. The stents were then examined angiographically and histologically at regular intervals. All stents were completely covered with endothelialized neointima in 3 weeks. There was no difference in intimal thickness between the stenotic and nonstenotic renal arteries. A large stent diameter and a large open or nonmetal surface may cause less intimal hyperplasia, but nonturbulent, fast arterial flow is probably the most important factor in ensuring long-term patency of the vessel.

Angioplasty, Balloon

Salt-induced folding of sea urchin sperm chromatin.

We have studied the folding in solution of chromatin from sea urchin sperm, which has the longest reported nucleosome repeat length (approximately equal to 240 base pairs) and an H2B with a basic N-terminal extension. The same two size- and ionic-strength-dependent transitions in sedimentation behaviour are observed as for other chromatins (rat liver, chicken erythrocyte) with shorter DNA repeat lengths. The results support the notion of an essentially similar folding of chromatins with different linker lengths of 0-80 base pairs. We interpret the hydrodynamic data in terms of a solenoid with about six nucleosomes per turn, which has greater stability in sea urchin sperm than in the other cases. The higher values of the sedimentation coefficients for sea urchin sperm oligomers indicate lower frictional coefficients, which probably result from accommodating the additional linker DNA and the extra mass of larger H1 and H2B in the central hole and/or the surface interstices of the solenoid.

Animals

Pancreatic sonography: enhancement by metoclopramide.

Abdominal sonograms were obtained before and after intravenous metoclopramide administration in 25 patients with a wide variety of abdominal complaints. Visualization of the pancreas was improved by this pharmacologic treatment in 44% of those patients in whom gas obscured the pancreatic bed. There was no improvement when fat was the primary prevention of visualization of the pancreas. There were no significant side effects of metoclopramide administration.

Adipose Tissue

Histone H5 promotes the association of condensed chromatin fragments to give pseudo-higher-order structures.

We describe two distinct situations in which chicken erythrocyte chromatin fragments associate in solution. The erythrocyte-specific histone H5 is implicated since chromatins that do not contain H5 do not show this behaviour. Well-defined oligomers of between approximately 6 and approximately 18 nucleosomes prepared at low ionic strength condense and associate when the ionic strength is raised to 75 mM, forming pseudo-higher-order structures. The associated forms, probably predominantly dimers, are stabilized by migration of about 10% of the H5, and of the minor lysine-rich histone H1, from the non-associated forms, probably reflecting the preference of H5 for higher-order structures observed previously [Thomas, J. O. and Rees, C. (1983) Eur. J. Biochem. 134, 109-115]. Since the final (H1 + H5) content of the aggregate at 75 mM is never higher than that of the fragment prepared at low ionic strength, migration is probably to a small proportion of sites that have inevitably become vacant due to handling losses at the higher (but not at low) ionic strength. H5 thus maximizes its interactions in the condensed state of chromatin and even maintains the association of two or more fragments without continuity of the DNA. Aggregates of oligomers larger than about 18 nucleosomes may be too long to withstand hydrodynamic shear forces in the absence of such continuity. During nuclease digestion of nuclear chromatin, H5 and, to a lesser extent, H1, are released from the ends of very short fragments and bind to larger oligomers of various sizes leading to heterogeneous aggregates that survive exposure to low ionic strength. These aggregates, in contrast to those described above, have up to 60% more H5 and 20% more H1 than chromatin prepared at low ionic strength. Whether the excess H5 and H1 bind non-specifically or to a second low-affinity binding site on each nucleosome is not known. The associated forms described above (1) are well defined and potentially useful for structural studies, whereas the other aggregates (2) seem less likely to be directly relevant to the native structure of chromatin.

Animals

Isolation of parietal cells from guinea-pig gastric mucosa and the immunological characterization of their antigenic structure.

A method is described for the isolation of parietal cells from the gastric mucosa of the guinea pig by enzymatic digestion with collagenase. A suspension was obtained that contained 70-80% parietal cells. About 80% of the cells were viable immediately after incubation, but viability dropped sharply after one hour. Parietal cells were identified by their morphology on light and electron microscopy, by their uptake of neutral red, by immunofluorescent staining and by carbonic anhydrase activity. Antibodies to four distinct parietal-cell antigens were obtained from rabbits immunized with the isolated parietal cells or fractions thereof. These antibodies were directed against the microsomal fraction of the parietal-cell cytoplasm, the plasma and nuclear membranes, the soluble proteins, and Castle's intrinsic factor. The antibody against the microsomal fraction, though reacting in the same way as the antibody to parietal cell canaliculi found in the serum of patients with pernicious anaemia, showed greater species specificity.

Anemia, Pernicious