Search PubMed⌕ Search

Biomedical subjects

E R Lee

Publications and source records attributed to E R Lee.

At least 73 records · Page 4Linked to original sources

Dynamic histology of the antral epithelium in the mouse stomach: I. Architecture of antral units.

The architecture of the pure mucous units of the pyloric antrum was investigated in 3- to 4-month-old CD1 mice. Units were serially cut in cross section and stained by a method combining the periodic acid-Schiff sequence, a modified Grimelius's silver nitrate procedure, and Regaud's hematoxylin. A total of 195 units were then reconstructed. Of these, six were cast in polyester resin and 189 were two-dimensionally reproduced on graph paper. The reconstructions showed antral units to be divided among three main classes. The first class, which contained 32% of the units, consisted of fingerlike tubules referred to as "singlets." Three types of singlets were observed. The first or type A, which represented 76% of the singlets, was divisible into three successive portions: a pit (foveola) opening onto the mucosal surface and lined by mucous cells referred to as pit cells, an isthmus continuous with the pit and containing immature proliferative mucous cells, and a gland forming the blind end of the tubule and lined by mucous cells referred to as gland cells. Type B (14% of singlets) was similar to type A except that its gland was forked. Type C (10% of singlets) differed by the absence of a gland. The units of the second class, which contained 53% of the total number, were joined together along part of their length and were named "multiplets." Most of them (90%) were organized into clusters of two, and 10% into clusters of three. In the joined portion, the epithelial cells of the adjacent units were in contact through junctional complexes and, therefore, were not separated by basement membranes. Otherwise the units showed the same component parts as in singlets. Also, as in singlets, the majority of the units were type A and a few were type B or C. The units of the third class, or "intermediates," consisted of tubules which exhibited a branching process. This process was of variable length but could include gland, isthmus, and sometimes pit. Thus, the process duplicated a varying proportion of the unit. In conclusion, the pure mucous units of the antrum exhibit various patterns which have been designated singlet, multiplet, or intermediate. It is proposed that these three patterns are related and represent temporal differences in the duplication and production of new units. Based on this assumption, a model has been elaborated to depict the likely sequence in the proliferation of pure mucous units. It is proposed that this proliferation takes place in the antrum of young adult mice.

Animals↗

Dynamic histology of the antral epithelium in the mouse stomach: II. Ultrastructure and renewal of isthmal cells.

The isthmus of typical mucous units of the pyloric antrum was investigated in 3- to 4-month-old CD1 mice using light and electron microscopy as well as 3H-thymidine radioautography. On the average, the isthmus measured 25 microns in length and was composed of 36 isthmal cells and two enteroendocrine cells. Isthmal cells generally displayed features found in embryonic cells, such as many free ribosomes, scant organelles, and a large reticulated nucleolus, and were, therefore, at an immature stage of development. Isthmal cells could be devoid of secretory granules ("granule-free cells," 2%) or contain a few small, spherical, PA-Schiff-positive, mucous granules in their apex. The granules in some of the cells had a variegated appearance and a diameter averaging 235 nm ("mottled granule cells," 39%); in other cells, the granules had a large diameter, 278 nm, with a pale background and a dense core ("core granule cells," 28%); while in still others they were homogeneously dark and measured 264 nm ("dense granule cells," 12%). Finally, some cells included a mixture of core and dense granules ("mixed granule cells," 14%). One hour after a single injection of 3H-thymidine, 37% of the isthmal cells were labeled. Each of the five isthmal cell types could acquire label and, therefore, divide. After one or more days of continuous 3H-thymidine infusion, all isthmal cells were labeled. Their turnover time was estimated to be 16.1 hr (t1/2 = 11.2 hr). The isthmus is thus composed of several cell types which are turning over rapidly. While all are relatively immature, the various types are thought to represent different developmental stages in the life history of an isthmal cell. A model devised on this basis proposes that the granule-free cells are stem cells, from which mottled granule cells are derived. These in turn evolve into either the dense granule cells of the upper isthmus or the core granule cells of the lower isthmus, or into the mixed granule cells (which are believed to develop eventually into dense granule cells or core granule cells). Maintenance of a steady state requires that the rapid production of isthmal cells be associated with rapid emigration; the dense granule cells presumably going to the pit and the core granule cells to the gland. The turnover of isthmal cells is accordingly described as following a "bidirectional pattern" of renewal.

Animals↗

Dynamic histology of the antral epithelium in the mouse stomach: III. Ultrastructure and renewal of pit cells.

The pit (foveola) of typical mucous units of the pyloric antrum was investigated in 3- to 4-month-old CD1 mice, using light and electron microscopy, sometimes combined with 3H-thymidine radioautography. Reconstruction of units from serial sections revealed that, on the average, the pit measured 151 microns in length and was lined by 184 mucus-containing pit cells. Of these, 164 were located along the wall of the pit, whereas 20 surrounded its opening on the free surface. For ultrastructural examination the pit was divided into equal thirds. The proximal third, located next to the isthmus and referred to as pit base, was composed of cells showing electron-dense mucous granules greater in number but similar in density and diameter to those of isthmal dense granule cells. Nucleoli were rather large, irregular, and reticulated; these and other features were indicative of partial differentiation. The appearance of the cells gradually changed with the distance from the isthmus. In the middle third or mid pit, cells had small, fairly rounded nucleoli, while mucous granules were more numerous than in the pit base but similar in appearance and size; these cells were considered to be mature. In the distal third or pit top-surface, granules became elongated and nucleoli shrank, and lysosomes and vacuoles greatly increased in number, indicating that cells were at a terminal stage. Indeed, some of the cells were extruded into the stomach lumen while others were phagocytosed by adjacent cells. Following a single injection of 3H-thymidine, labeling was found only in a small cohort of cells in the pit base. At the end of 1 day of continuous infusion, the cohort of labeled cells had reached the mid pit; by 2 days, the pit top; and by 3 days, the free surface, where cells were eventually lost. The renewal time of pit cells was assessed at 2.98 days (t1/2 = 1.8 days), giving a turnover rate of 33.5% per day. It is estimated that the divisions of pit base cells provide two-thirds of the cells needed daily for pit-cell renewal, while the other third is supplied by an influx of dense granule cells from the isthmus. These cells enter the pit and continuously migrate toward the gastric lumen, while differentiating in the pit base, maturing in the mid pit, and reaching a terminal stage at the pit top-surface. The progressive and orderly migration of pit cells is described as a "pipeline pattern" of renewal. It is completed in about 3 days when terminal cells are lost at the pit top-surface.

Animals↗

Dynamic histology of the antral epithelium in the mouse stomach: IV. Ultrastructure and renewal of gland cells.

The renewal of gland cells was investigated by three-dimensional reconstruction of typical mucous units of the pyloric antrum using electron microscopy and 3H-thymidine radioautography in 3 to 4 month-old CD1 mice. Based on analysis of 42 units, the average gland measured 31 micron in length and was composed of 37 (mucous) gland cells with eight enteroendocrine cells scattered among them. The gland neck cells located close to the isthmus showed the cytoplasmic and nuclear features characteristic of differentiating cells. The mid-gland cells occupying the central portion of the gland appeared to be at a more advanced stage of development and completing differentiation. The gland base cells comprising the blunt end of the gland were fully mature. To quantify the renewal process, the percent of gland cell nuclei carrying label was determined at several times following 3H-thymidine administration. The rate of proliferation was found to be greatest in the gland neck, lower in the mid-gland, and even lower within the gland base. Furthermore, the isthmus contributed to gland-cell renewal by providing an estimated 12.4 cells per day. Labeled cells migrated toward the blunt end of the gland. The migration rate became progressively slower with their descent, and many cells were lost along the migration pathway, mainly in the gland neck. The loss took place without being preceded by gradual cell degeneration, but occurred as a result of rapid extrusion to the lumen or, less frequently by pyknosis, which could be followed by phagocytosis. It is concluded that the rapid rate of mitosis within the isthmus and gland neck generates a pressure causing downward migration of the cells toward the blunt end of the gland. The rate of migration, however, gradually diminishes as cells descend into the gland, presumably owing both to decreasing proliferation rate and to cell loss. Thus, while cells migrate down toward the gland base, many are lost before reaching it. This sequence is described as "the cascade pattern" of renewal.

Animals↗

Direct temperature measurement.

Hyperthermia has little hope of progressing as a clinical modality without accurate assessment of the temperature distributions obtained. At the present time only direct, invasive temperature-measuring techniques are possible, posing severe limitations. Established techniques for clinical temperature measurement have developed over the past few years, and for both ultrasound and electromagnetic hyperthermia it is possible to get temperature-time profiles at a large number of spatial points. Position uncertainty, thermal conduction smearing, and artifactual heating limit the accuracy to about 0.2 degrees (electromagnetic) or 0.5 degrees (ultrasound), but this is probably less of a hindrance than the inadequate percentage of tumor and normal tissue volume for which achieved temperatures can be documented.

Body Temperature↗

Anatomical site-specific modalities for hyperthermia.

The clinical application of hyperthermia in the treatment of deep-seated tumors remains an empirical science. The pleomorphic nature of the neoplasms and the great diversity in the anatomy and physiology of the individual tumor locations make the treatment of nearly every neoplasm a unique challenge. A wide variety of devices is required, both for the administration of hyperthermia and for the measurement of the temperatures achieved. At Stanford University, these include the BSD Medical Corp. annular phased array system, an isospherical ultrasound device, and interstitial radiofrequency for deep heating. Ultrasound transducers and a variety of microwave applicators are used for superficial hyperthermia. Six illustrative case studies, selected from the 91 patients treated in our program since October 1981, are presented, with discussion and comparison of treatment devices. Difficulties in deep heating were encountered in several instances, believed secondary to the thickness of the s.c. fat, the relatively high heat-induced tumor blood flow, and the presence of adjacent bone. It is suggested that ultimate improvement in clinical results will be possible once a better understanding is achieved of such anatomical and physiological factors.

Adenocarcinoma↗

Division of the mouse gastric mucosa into zymogenic and mucous regions on the basis of gland features.

The stomachs of adult CD1 mice were investigated by anatomical examination and light microscopy. Serial sections were prepared of entire stomachs; the various types of gastric glands were characterized; and, using every 30th or 60th serial section, maps of gland distribution were obtained through point-plotting serial reconstruction. Gross examination shows that the cephalic third of the stomach consists of a thin-walled, domelike structure, the forestomach. The rest of the organ, or stomach proper, is subdivided into two parts, the thick-walled corpus, which approximately occupies the middle third, and the less vascular pyloric antrum which forms the remaining caudal third of the organ. Histologically, glands are absent from the forestomach mucosa but are numerous throughout the stomach proper. They are of two main types, namely, zymogenic glands, which contain, among others, zymogenic cells, and mucous glands, which lack these cells but contain mucous cells. Both gland types show a few enteroendocrine cells. Moreover, some of the mucous glands include parietal cells (mucoparietal glands), while others do not (pure mucous glands). Mucosal maps reveal that the glands of each type are located in distinct areas of the mucosa. Thus a compact zymogenic region may be defined, occupying 56% of the glandular mucosa and containing only zymogenic glands. The mucous region, on the other hand, composed only of mucous glands, is extensive and divided into a narrow cephalic band (5.2% of the glandular mucosa) and a large caudal part (38.8%). Along the lesser curvature these parts are continuous, and together they encapsulate the zymogenic region. In proximity to the border of this region, and only there, do the mucous glands include parietal cells. A comparison of mucosal maps and gross features indicates that the corpus includes both the zymogenic region and the cephalic band of mucous glands, whereas the antrum is composed entirely of the mucous glands of the caudal part.

Animals↗

Hemorrhagic erosive gastritis. A clinical study.

Four hundred consecutive patients, in a representative Southern California population, hospitalized for upper gastrointestinal hemorrhage, had endoscopic examinations performed within 24 hours of arrival in the emergency room. Seventy-four (18.5 percent) of these were found to have the typical lesions of acute hemorrhagic erosive gastritis. The clinical spectrum of this group is examined and a comparison made with a Veterans Hospital population reported previously.

Adult↗