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Biomedical subjects

W J Cliff

Publications and source records attributed to W J Cliff.

At least 37 records · Page 2Linked to original sources

The aortic tunica media of the developing rat. I. Quantitative stereologic and biochemical analysis.

The tunica media of thoracic aortas from female rats in age from newborn to 12 weeks were analyzed quantitatively by using stereologic techniques in the electron microscope. Collagen, elastin, smooth muscle, myofilaments, Golgi apparatus, ergastoplasm, and surface to volume ratios were among those components quantified. These parameters were correlated with measurements of medial thickness, blood pressure, and tangenital tension in the wall and with biochemical estimates of collagen and elastin. A progressive increase in morphologically recognizable collagen in the media was in parallel with the increasing tangenital wall tension. Biochemical analysis indicated the presence of much soluble collagen in the early stages of development. Elastin was the major component contributing to increasing wall thickness. The elastin laminae were completely formed by 4 weeks of age, but further elastin was laid down as branches extending between medial cells in the aortas of animals between 2 and 12 weeks of age. Smooth muscle cells were ovoid in young animals and contained large amounts of ergastoplasma and Golgi apparatus, but very few myofilaments. With advancing age, these cells became irregular in outline, and their surface to volume ratios doubled. The myofilament volume increased greatly during development, associated with a decrease in "undifferentiated" cytoplasm, ergastoplasm, and Golgi apparatus. The maximal development of the latter two organelles was coincident with large increases in the connective tissue components.

Animals↗

The aortic tunica media of the developing rat. II. Incorporation by medial cells 3-H-proline into collagen and elastin: autoradiographic and chemical studies.

Four-week-old rats received intraperitoneal injections of 3-H-proline, and their thoracic aortas were removed at various times after injection. Autoradiography at the electron microscopic level was carried out on this tissue, together with isolation and chemical analysis of tritiated proline and hydroxyproline from procollagen, and elastin fractions. Autoradiograpic results were expressed in terms of tissue component volumes as calculated by morphometry. Autoradiographic grains were concentrated over medial cells 15 minutes after injection of label. By 30 minutes after injection some extracellular label was present as well; at 3 hours postinjection, large numbers of grains were found overlying cell surfaces, as well as over collagen and elastic fibers. Most grains were present over collagen and elastic tissue 10 hours after injection, although some intracellular labeling persisted. On a grain per unit volume basis, intracellular label steadily decreased over the time interval studied. Collagen showed maximal labeling at 3 hours, but elastic tissue labeling increased up to 10 hours postinjection. Chemical isolation of 3-H-proline and 3-H-hydroxyproline from the three fractions showed that incorporation of label into collagen and elastin is, on a time basis, consistent with autoradiographic labeling and that the labeling products are, in fact, these proteins, to the exclusion of nonspecific labeling.

Animals↗

A study of allograft kidney rejection occurring simultaneously in whole organ and ear chamber grafts in the rabbit.

When portions of adult renal tissue are allografted into the rabbit ear chamber, they usually survive for periods of up to several months (6). When a kidney from the same donor is grafted as a whole organ, the ear chamber grafts then reject with the whole organ in 7 days. During that time serial needle biopsies of the whole organ are compared with the in vivo appearance of the ear chamber grafts. This establishes that the changes occurring in the ear chamber grafts are monitoring the rejection process proceeding in the whole organ grafts. Dramatic vascular changes herald the earliest stages of unmodified rejection. A highly characteristic form of individual discrete platelet adhesion to both endothelium and adherent leukocytes is observed which is associated with the release reaction. At times as many as 20 such discrete platelets are clearly visible in profile in one high-power field. This demonstrates in vivo a mechanism whereby vascular and parenchymal damage may be produced by platelet contents, without previous aggregation or thrombus formation being necessary.

Animals↗

Observations on tissue grafts established in rabbit ear chambers. A combined light and electron microscopic study.

An in vivo microscopic and ultrastructural study of tissues transferred to the transparent rabbit ear chamber is presented. Fragments of liver, kidney, thyroid, and myometrium were successfully auto- or allografted into the chamber from donors of all ages and allowed continuous in vivo observation of parenchymal structure and function, as well as of the graft vasculature which plays such an active role during rejection. Circulation was quickly reestablished by anastomosis of graft vessels to those of the ear chamber membrane and only minor reversible parenchymal changes occurred. Both vessels and parenchyma retained the characteristics of the organs of origin on both light and electron microscopy and were observed functioning in vivo for periods up to 1 yr in the case of autografts, and until rejection occurred in allografts. In the latter case, rejection did not occur in tissues obtained from adult and neonatal donors for nearly 3 months, while tissues of fetal origin were generally rejected much earlier. The kidney grafts provide a unique opportunity for a close comparative study of mammalian fetal and adult glomerular blood flow under varying rates of perfusion, and the tubular epithelium could be observed regenerating after initial acute tubular necrosis. Renal tubules from fetal, neonatal, and adult donors were all capable of metaplastic change to form a highly ciliated epithelium. Grafts of these tissues will allow the fine detail of the processes of rejection to be studied continuously in vivo.

Age Factors↗