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Biomedical subjects

R P Thompson

Publications and source records attributed to R P Thompson.

At least 19 recordsLinked to original sources
PubMed1992

Immunolabelling patterns of gap junction connexins in the developing and mature rat heart.

The distribution of gap junctions in prenatal, postnatal, and adult rat hearts was studied by laser scanning confocal microscopy, using antiserum raised to a peptide (HJ) matching part of the sequence of connexin43 (a cardiac gap junction protein). Using digital reconstruction of optically-sectioned tissue volumes, a highly sensitive detection of immunolabelled gap junctions was achieved. The distribution of positive anti-HJ immunolabelling was regionalised in the prenatal heart from its first detection at 10 days post-coitus. High levels of immunopositive staining occurred in the trabeculae of the embryonic ventricles. Other zones of the early myocardium including early central conduction tissues had no detectable signal. The prenatal outflow tract, interventricular septum and a narrow zone of myocardium subjacent to the epicardial free wall also had low levels of immunopositive signal. During postnatal growth and in the adult rat heart, a marked distinction emerged between the central conducting tissues of the atria and ventricles. Whilst small immunostained gap junctions became detectable within the atrioventricular node on the atrial side of the junction, between the interatrial and interventricular septa, no immunolabelling was found within the ventricular branching bundle. This difference between the atrioventricular node and branching bundle is consistent with potential functional distinctions between these two structures, and is not consistent with the recent proposal that the His bundle and its branches act as an extended atrioventricular node in smaller mammals such as the rat. Ventricular Purkinje fibres, distal to the branching bundle, showed high levels of anti-HJ immunostaining. Organisation of gap junctions into intercalated disks within the ventricle proceeded late into intercalated disks within the ventricle proceeded late into the adolescent stages of heart growth. The distribution of a second connexin protein, MP70, not previously characterised in the heart, was studied using monoclonal antibodies. MP70 was transiently immunolabelled in the heart during the postnatal period, but only within valves. Previously, this protein has been reported only in the eye lens. MP70-containing gap junctions may represent a specialisation in avascular tissues, since blood vessels are not present in either the eye lens or the cusps of heart valves.

Animals↗
PubMed1992

A two-step alignment method for 3D computer-aided reconstruction based on fiducial markers and applied to mouse embryonic hearts.

An accurate three dimensional computer reconstruction of microscopic biological objects or distribution of molecules identified on serial sections must solve two major problems: 1) the alignment of sections using adequate extrinsic references (fiducial markers); 2) the impossibility of observing these references and the cellular or molecular structures in the microscope at the same magnification. To provide extrinsic references for objects embedded in soft media, we have modified and simplified the charcoal-paraffin method described by Langemeijer and Simons (1973). It consists of drilling three or four small holes into the paraffin block, sealing this block at the extremity of a glass holder and, from the other extremity of the holder attached to a rubber hose, aspirating a liquefied mixture of charcoal-paraffin to fill these cylindrical holes. An alignment procedure was developed using serial sections of mouse embryonic hearts with bromodeoxyuridine-labelled DNA synthesizing cells. From each fourth section, two sets of contours have been drawn and digitized: 1) at low magnification (about 40x), embryo body wall, heart, neural tube and extrinsic reference marks (black dots); 2) at higher magnification (240-300x): heart contours alone (without extrinsic references, but with individual labelled cells). Different operations of the computer-aided alignment, as well as checking of results by inverse alignment, are described in detail. This two-step alignment method offers a practical, efficient compromise between: a) purely subjective alignment based only on tissular landmarks interpreted by the operator; b) ideal perfect alignment based not only on adequate references, but on computerized correction of section deformation, as well.

Animals↗
PubMed1979

Liver disease among homosexual males.

5% of 2612 homosexual males attending genitourinary clinics were found to be hepatitis-B surface-antigen (HBsAg) positive. Liver biopsy was done in 25 who had abnormal liver-function tests but no symptoms or signs of liver disease, and 14 (56%) of these proved to have chronic active hepatitis or active cirrhosis. Neither the liver-function tests nor the viral markers in serum reflected the severity of the liver disease. 38% of a group of 118 HBsAg positive patients were HBeAg positive, and sexual contacts of these individuals may be at serious risk of infection.

Carrier State↗
PubMed1979

Morphogenesis of the truncus arteriosus of the chick embryo heart: the formation and migration of mesenchymal tissue.

The appearance and migration of mesenchymal cushion tissue within the truncus arteriosus of the normal 2.5 to 6-day chick embryo heart was surveyed systemically with the light microscope. Series of cross-sections taken from replicate hearts at successive developmental stages allowed comparison of the following qualitative and quantitative aspects of early truncal morphogenesis. Mesenchyme within the truncus was derived from two distinct sources. The first mesenchyme appeared to migrate caudally into the cardiac jelly of the distal truncus from the nearby aortic arch region, coincident with slowing of the anterior elongation of the heart tube (Hamburger-Hamilton Stage 17-18). A second, separate mesenchymal population, derived from endocardium, began to fill the conus and proximal truncus in a radial direction, coicident with expansion of the bulbs cordis (Stage 12-19). The measured kinetics of relative cell numbers, distributions, and mitotic indices suggest substantial contributions from both sources. By Stage 26, the conotruncal region was filled with mesenchyme, which then condensed to form the anlagen of three future structures: the semilunar valves, the aorticopulmonary septum, and the tunica media of the great arteries.

Animals↗
PubMed1979

Morphogenesis of the truncus arteriosus of the chick embryo heart: tissue reorganization during septation.

Septation of the truncus arteriosus of the normal chick embryo heart was surveyed systematically with the light microscope. Tissue from replicate samples at successive periods of development was sectioned within an arbitrary coordinate system based on positional reference points along the external surface of the heart. Correlation of several aspects of tissue morphology within this spatial and temporal reference-frame yielded a new description of tissue associations and kinetics during septation. A stable complex of tissue structures appeared in the downstream, distal truncus at Stage 25 and persisted throughout the septation process. This complex consisted of (1) the cephalic margin of the myocardial sheath, and (2) the adjacent bifurcation of the vascular lumen, linked together by (3) the newly condensed Y-shaped strap of cells forming the aorticopulmonary septum. The apparent motion of this septation-complex toward the ventricle(s), the appearance within the thoracic cavity of the adjacent segments of the aortic arches, and measures of tissue length and width suggested that septation was accompanied, and perhaps initiated, by increased tension along the truncus. The truncal ridges remained upstream from the complex, with mesenchymal condensations beneath the endocardium differentiating into the definitive semilunar valves. Downstream from the bifurcation, mesenchyme in the aortic arch region condensed around the separate lumens to form the smooth muscular tunica media of the great arteries. The epicardium developed in a caudocephalic direction along the heart tube. Vagal innervation approached the heart cephalocaudally. Capillaries formed along the dividing truncus in both directions. Autoradiography following 3H-thymidine labelling demonstrated reduced DNA synthetic activity in the cephalic margin of the myocardium and aorticopulmonary septum, compared with the associated loose mesenchyme.

Animals↗
PubMed1979

Treatment of osteomalacia associated with primary biliary cirrhosis with parenteral vitamin D2 or oral 25-hydroxyvitamin D3.

The histological and biochemical response of osteomalacia has been studied in four patients with primary biliary cirrhosis, who were treated with oral 25-hydroxyvitamin D3, 50 microgram daily, or intramuscular vitamin D2, 150,000 units once weekly, for five to 12 months. All patients showed complete histological healing of osteomalacia, despite rapidly deteriorating liver function in three. Plasma 25-hydroxyvitamin D concentrations were low in all patients before treatment, but became normal during either vitamin therapy. Serum calcium and phosphate levels, and urinary calcium excretion were not always reliable in predicting the histological response to treatment. Serum alkaline phosphatase activity decreased in all patients during vitamin D therapy. We conclude that both high-dose parenteral vitamin D2 and oral 25-hydroxyvitamin D3 may be effective in healing osteomalacia associated with primary biliary cirrhosis. Measurement of plasma 25-hydroxyvitamin D levels during vitamin D therapy provides useful information about 25-hydroxylation of the parent vitamin and intestinal absorption of orally administered 25-hydroxyvitamin D3.

Administration, Oral↗
PubMed1979

Collagen synthesis in the developing chick heart.

We have surveyed the amount and types of collagen synthesized in two regions of the chick heart during embryonic development. Cardiac tissues from successive periods of development were labeled with 3H-proline in short-term organ culture. The fraction of incorporated label present as collagen was estimated by comparison of TCA-soluble radioactivity before and after digestion with purified bacterial collagenase. This measure of collagen synthesis varied only slightly with the length of the labeling period and agreed with values obtained by labeling in ovo. In the developing outflow tract, the fraction of label present as collagen increased sharply during the period of truncal septation (5-9 days), rising from initial values of 6% at 3 days of incubation to a plateau of about 25% (10-19 days). In ventricular myocardium, this fraction rose gradually from 3 to 20% between 3 and 19 days of incubation. The types of collagen synthesized in developing heart were analyzed by limited pepsin digestion and acrylamide gel electrophoresis, using collagens synthesized in tendon, cartilage, skin, and lens capsule for comparison. The types of collagen synthesized in both cardiac regions changed in similar manner during development. During the first week of cardiac function, a substantial but progressively smaller fraction of total collagen synthesized was identified as Type IV. Synthesis of Type I collagen increased sharply during this period and predominated during the second half of development. Type III collagen was synthesized in trace amounts by the middle of development and constituted approximately one-sixth of total collagen synthesis just before hatching. Minor amounts of collagen identified as Type B collagen were synthesized throughout the latter two-thirds of development.

Animals↗
PubMed1979

Matrical ordering in the morphogenesis of tunica media.

The cells which will form the smooth muscle tunica media are derived embryologically from the cardiac mesenchyme referred to as endocardial cushion tissue. These progenitor smooth muscle cells, however, are derived primarily from aortic arch mesenchyme as opposed to the endocardium in the prevalvular areas. The matrical microenvironments of these cells begin to change at approximately 5 days of development when the progenitor smooth muscle cells acquire a more fibrillar matrix. The prospective adventitia and valvular areas still maintain an environment rich in hyaluronate and proteoglycans. By Day 6, the 110Ao microfibril, characteristic of smooth muscle cells, appears in the matrix well in advance of the amorphous elastin component seen at Days 8 and 9. The orientation of the collagenous microfibrils and elastic microfibrils is non-random with respect to the layers of cells, and this precludes a simple substrate alignment model in establishing the characteristic laminarity of this tissue.

Animals↗
PubMed1978

[1-14C]Ethanol breath test in alcoholic liver disease.

The activity of ethanol metabolising enzymes was assessed in 51 patients with alcoholic and non-alcoholic liver disease using tracer doses of [1-14C]ethanol and measuring 14CO2 excretion in the breath. Alcoholic patients with only fatty infiltration of the liver showed significantly increased activity compared with controls. Comparing alcoholic patients with cirrhosis and a serum albumin greater than 28 g/l, activity in those with a recent history of continued heavy drinking was significantly greater than in patients who had abstained from alcohol. In addition, both groups of alcoholic cirrhosis showed significantly more activity than patients with non-alcoholic cirrhosis. The activities of patients with acute alcoholic or viral hepatitis were normal when their prothrombin times were less than 7 sec prolonged, but were reduced when prolongation exceeded 7 sec. These results demonstrate that in chronic alcoholic liver disease, even with cirrhosis, alcohol can still increase the activity of ethanol oxidising enzymes provided hepatic function remains adequate. However, this response is lost in acute liver damage and in chronic alcoholic disease with severe hepatic dysfunction.

Albumins↗
PubMed1978

Lead, copper, and cadmium in teeth of normal and mentally retarded children.

Whole teeth obtained from handicapped children and from controls have been analysed for lead by anodic stripping voltammetry. No significant differences were found between the two groups. Teeth originating from the same patient showed systematic variations in lead content that are dependant on anatomical tooth type. The nature of this association is discussed. Analyses of sectioned teeth revealed, for cadmium and copper, unexpectedly large variations. High concentrations of cadmium found in the tips of deciduous incisor teeth indicate a probable contribution from maternal blood.

Cadmium↗
PubMed1978

The prevalence and severity of major disabling conditions--a reappraisal of the government social survey on the handicapped and impaired in Great Britain.

This paper re-examines the data gathered for the Government Social Survey on the Handicapped and Impaired in Great Britain. The underlying cause of disablement is considered in conjunction with severity and prevalence. When these are taken together a picture emerges in which stroke, arthritis, and circulatory disorders are the most frequent cause of severe disability in the community. An attempt is also made to examine the way in which the survey might be biased by the non-inclusion of those in institutions.

Adult↗
PubMed1978

Kinetics of 14C-glycocholic acid clearance in normal man and in patients with liver disease.

The plasma clearance of a tracer dose of 14C-glycocholic acid, and fasting total serum bile acid concentrations were measured in 14 control subjects and in 38 patients with acute and chronic liver disease. In controls plasma clearance was 415 +/- 24 ml min-1 m-2 (mean +/- SEM), equivalent to a 'first-pass' extraction by the liver of 85%. Clearance was not significantly different from controls in patients with acute hepatitis or active chronic hepatitis, nor in anicteric patients with primary biliary or alcoholic cirrhosis. Thus bile acid clearance was impaired only in icteric chronic liver disease. In contrast, serum bile acid concentrations were abnormal in all but seven patients, six of whom had active chronic hepatitis in complete biochemical remission. The pattern of plasma disappearance of injected 14C-glycocholic acid was biexponential in controls and patients with liver disease, and computer analysis of the curves suggested that there was significant distribution of bile acid outside the vascular space. The preservation of bile acid clearance in anicteric chronic liver disease confirms that it is dependent more on liver blood flow than on liver cell function.

Adult↗