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PubMed1978

Long term effect of cis-diamminedichloride platinum (CDDP) on renal function and structure in man.

To examine CDDP induced nephrotoxicity in patients with testicular carcinoma, we measured renal function prior to therapy and at six month intervals for twelve months in fifteen patients and twenty-four months in seven patients. CDDP was given iv at 20 mg/M2 per day for five days at three week intervals. Eight patients received three courses, four received four courses and three received more than four courses. The mean creatinine clearance +/- SD prior to treatment was 112 +/- 12 ml/min. By six months, it had decreased to 68.5 +/- ml/min (p less than 0.01) and it remained at that level. Plasma creatinine and blood urea nitrogen increased significantly. Subjects receiving other potential nephrotoxins in addition to CDDP developed a greater decrease in creatinine clearance (p less than 0.05). Proteinuria and functional tubular disturbances were not observed. Microscopic features were characterized by hydropic degeneration of the renal tubular epithelium, thickened tubular basement membranes and mild interstitial fibrosis. Electron microscopy revealed phagolysosomes filled with flocculent material. CDDP resulted in a permanant, nonspecific renal injury in our patients. Although the renal injury has remained subclinical, future courses of CDDP may lead to clinically important chronic renal failure.

Adolescent↗

PubMed1981

Electron microscopy in the diagnosis of malignant schwannoma.

Fifteen malignant schwannomas were examined by light and electron microscopy. Five tumors arose in patients with neurofibromatosis and five were contiguous with a peripheral nerve (Group I). Five tumors met neither of these generally accepted diagnostic criteria but were light microscopically seen as compatible with malignant schwannoma when examined under light microscope (Group II). In the better differentiated areas of Group I lesions, long, overlapping, tightly packed cytoplasmic processes were parallel to homogeneous flocculent material, occasionally assuming a linear appearance suggesting basal lamina. In Group II, similar cytoplasmic processes were present but the extracellular material was less extensive and had a less obvious relationship to the plasma membrane. In neither group were fine intracytoplasmic filaments prominent. Malignant schwann cells are seldom as ultrastructurally differentiated as their benign counterparts. Nevertheless, within the context of well-studied light microscopy and the sampling error inherent in ultrastructural examination, electron microscopy can support the diagnosis of malignant schwannoma.

Adult↗

PubMed2000

A proteomic approach for the study of Saccharomyces cerevisiae cell wall biogenesis.

In fungi, cell shape is determined by the presence of a rigid cell wall which separates the cell from the extracellular medium. This highly dynamic structure is essential for the maintenance of cell integrity and is involved in several phenomena such as flocculation, adherence and pathogenicity. The composition of the fungal cell wall is well known, but issues such as the assembly and remodeling of its components remain poorly understood. In an attempt to study the de novo construction of the yeast cell wall, we have undertaken a large-scale proteomic approach to analyze the proteins secreted by regenerating protoplasts. Upon incubation of protoplasts in regenerating conditions, numerous proteins are secreted into the culture medium. These presumably include proteins destined for the cell wall, comprising both structural proteins as well as enzymes involved in cell wall biogenesis. This work reports the establishment of a reference map of proteins secreted by regenerating protoplasts by means of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and their identification by mass spectrometry. Thirty-two different proteins have been identified, including known cell wall proteins, glycolytic enzymes, heat shock proteins, and proteins involved in several other processes. Using this approach, novel proteins possibly involved in cell wall construction have also been identified. This reference map will allow comparative analyses to be carried out on a selected collection of mutants affected in the cell wall.

Amino Acid Sequence↗

PubMed1985

Morphology of the bovine epididymis.

The epididymis of the bull was divided into six regions, and morphological differences between regions were studied. The epithelium of all regions contained four cell types: principal and basal epithelial cells, and intraepithelial lymphocytes and macrophages. The epithelium of regions II-V also contained a few apical cells. Principal cells of all regions possessed an endocytotic apparatus including stereocilia underlain by canaliculi, coated vesicles, and subapical vacuoles (up to 1 micron in diameter); however, large vacuoles with a flocculent content and multivesicular bodies (up to 5 microns in diameter) were most numerous in regions II, III, and IV. The unique features of principal cells of region I were the presence of well-developed Golgi bodies, few lipid droplets, and whorls of smooth endoplasmic reticulum in the supranuclear cytoplasm. Numerous mitochondria, distended cisternae of rough endoplasmic reticulum, and dense granules characterized the infranuclear cytoplasm of the principal cells of regions II-VI; however, these features were more developed in region V. Apical cells were characterized by the apical location of the nucleus, many mitochondria in the apical cytoplasm, and few microvilli at the luminal border. Basal cells with few cytoplasmic lipid droplets were present throughout the length of the epididymis but appeared more numerous in region V. Intraepithelial lymphocytes were present at all levels of the epithelium but were never seen in the lumen. Intraepithelial macrophages containing heterogeneous granules, eccentric nuclei, and pseudopods were invariably seen near the basal area of the epithelium in all regions. These observations are discussed in an effort to define the role of each cell type in the epididymal epithelium.

Acid Phosphatase↗

PubMed1987

Immunohistochemical demonstration of keratins in the cysts of thyroid glands, parathyroid glands, and C-cell complexes of the dog.

Cyst structures were often detected in and around thyroid glands of the dog. The present study revealed the frequency of occurrence, the light microscopic features, and the immunoperoxidase reactions to anti-keratin and anti-19S-thyroglobulin antisera of each cyst located in parathyroid III, parathyroid IV, thymus IV, C-cell complexes, and thyroid parenchyma from 112 dogs. In each location, cysts showed characteristic features. In parathyroid III, the cysts were covered with single or pseudostratified epithelium composed of ciliated cells; whereas in parathyroid IV they were covered with keratinizing stratified squamous epithelium. In C-cell complexes, small cysts lined with small packed cells were predominant, and large cysts lined with single cuboidal cells or stratified squamous cells were also present. In thymus IV located in the close vicinity of parathyroid IV, cyst epithelium consisted of several types of cells showing variable features. In thyroid parenchyma, there were several types of cysts: some were covered with ciliated columnar cells, and others were covered with two or multilayers of small packed cells or cuboidal cells. In spite of these differences in appearance of the cysts located in different tissues, all their epithelia were immunoreactive to the keratin antisera, except for small cysts in C-cell complexes, which were regarded as immature structures. Thus, the presence of keratin filaments in epithelial cells seems to be a characteristic feature of all cysts. The lumens of each cyst contained variable amounts of amorphous materials, which showed colloid-like, flocculent, foamy, and granular features and were periodic acid-Schiff-positive in variable degrees, from weak to intense. Although the lumenal contents of the cysts in parathyroid III revealed no immunoreactivity for 19S-thyroglobulin, those in thyroid parenchyma, C-cell complexes, parathyroid IV, and thymus IV reacted strongly with the 19S-thyroglobulin antiserum.

Animals↗

PubMed1990

Occurrence of colloid-containing follicles and ciliated cysts in the hypophysial pars tuberalis from guinea pigs of various ages.

Colloid-containing follicles and ciliated cysts in the hypophysial pars tuberalis of guinea pigs at various ages ranging from 5 days to 36 months were examined by periodic acid-Schiff (PAS) reaction, immunohistochemistry, and electron microscopy. The follicles storing PAS-positive colloid were encountered in the pars tuberalis of all guinea pigs examined, although only a few were present in young animals. The follicles gradually increased in number with age. The largest number of follicles was found in the senile male group: 141.3 +/- 11.9, about 10 times the number in the 5-day-old male group. The follicles were scattered throughout the entire length of the pars tuberalis. Follicles with enlarged luminal cavities were concentrated in the ventral caudal region surrounding the infundibular stem and merges with the pars distalis. Three different types of follicles were found by electron microscopy: 1) those surrounded by nongranulated follicular cells that may correspond to the stellate-follicular cells in the pars distalis, 2) those surrounded by specific cells that were packed with vesicular inclusions, and 3) those surrounded by granulated cells that may be gonadotropes. In the follicles lined by non-granulated follicular cells, long, prominent microvilli and cytoplasmic processes protruding into the lumen and invaginations of colloid were often observed at the apical cell region. The follicles lined by the specific cells having numerous vesicles were localized only in the ventral caudal portion. The vesicles ranged from 200 to 700 nm in diameter, and the outer surface of their limiting membrane was partly studded with ribosomes. Gonadotropes immunoreactive to the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) antisera were distributed in the guinea pig pars tuberalis. As well as the typical follicles described above, the follicles composed solely of granulated cells showed microvilli protruding into the cavities and junctional complexes at the apical lateral surface. They stored heterogeneous materials in the lumina. Some secretory granules gave the appearance of being discharged into the lumen. Ciliated cysts were frequently observed in the pars tuberalis; their incidence was 71.7%. The ciliated cysts were much larger than colloid-containing follicles. Cystic cavities were only partly filled with heterogeneous materials showing colloid-like, flocculent, and granular features.

Aging↗

PubMed1991

Regional differences in the morphology of the goat epididymis: a light microscopic and ultrastructural study.

The goat epididymis, based on morphological differences, was divided into five regions; regions I and II, and the proximal part of region III constituted the head; the distal part of region III and region IV, the body; and region V, the tail. The epithelium of all regions contained principal and basal epithelial cells and intraepithelial lymphocytes and macrophages. In addition, regions II to IV also contained a few apical cells. Clear cells were absent. The epithelium varied in height from the tallest in region I (88 +/- 33 microns) to the shortest in region V (38 +/- 5 microns). Conversely, the luminal diameter, thickness of smooth muscle wall, and luminal sperm concentration were highest in region V. The irregular epithelial height of regions I and IV accounted for a stellate lumen in contrast to the oval lumen of the other regions. Whereas the lumen of region I contained only a few sperm, those of regions II, III, and IV were filled with sperm. Principal cells were the only cell type that showed striking cytological differences between regions. While they contained absorptive features (canaliculi, pinocytotic and coated vesicles, and subapical vacuoles) in all regions, the principal cells of region II were filled with large, heterogeneous vacuoles (up to 5 microns in diameter), suggesting that they may be preferentially involved in transporting and digesting particulate material. Besides absorptive features, principal cells of all regions contained morphological correlates of protein synthesis such as highly developed Golgi complexes in the supranuclear area and numerous cisternae of RER near the Golgi body and in the infranuclear cytoplasm. The cisternae of RER were more developed in region IV, and in some instances, they were distended with flocculent material resembling newly synthesized protein. Unlike the protein synthesizing organelles, principal cells of all regions lacked morphological correlates of steroid hormone synthesis. These results are compared with previously published data on the regional differences in the epididymis of other species, especially with those of the rat and the bull, in an effort to understand the significance of the epididymis in sperm maturation.

Animals↗

PubMed1995

Muscle cell death during the development of head and neck muscles in the chick embryo.

Degenerating myofibers have been reported in the embryos and neonates of a number of birds and mammals, but neither the pervasiveness of the phenomenon nor the spatio-temporal patterns of degeneration has been examined in detail. Using transmission electron microscopy, we determined the patterns of muscle cell death in the chick biventer cervicis, a head extensor muscle. Cell death is most pronounced at incubation days 10 through 15, and occurs throughout the muscle. This is the period during which many myofiber clusters segregate into individual fibers, each with a separate basal lamina, and secondary myofibers become demarcated. Cells of largest diameter, presumably the primary myofibers, are preferentially affected. Degenerating cells exhibit a cohort of cytological features consistent with apoptosis, including the presence of dense, darkly-staining, hypercontracted myofibrils, misshapen nuclei with irregular chromatin condensations along the nuclear envelope, and scores of cytoplasmic vesicles and vacuoles. In cross section some large diameter muscle cells are characterized by sparse, flocculent cytoplasm that is devoid of myofibrils and organelles. Some show disintegrating cell membranes. In longitudinal section 200-300 microns long regions of hypercontracted myofibrils alternate with areas devoid of fibrils; this arrangement suggests that the myofibrils break into segments that are in register along one part of a muscle fiber and entirely absent from the adjacent length of fiber. We have observed similar patterns of muscle cell degeneration in the complexus, splenius cervicis, depressor mandibulae, and branchiomandibularis muscles. By day 18 of incubation most signs of degeneration are absent and by hatching (day 21) the muscle fibers all appear healthy. Many of these cytological changes in embryonic head muscle cells are characteristic of programmed cell death. We hypothesize that large-scale death of myocytes is a normal part of avian myogenesis and an important mechanism for affecting the transformation from embryonic to hatching muscle patterning.

Animals↗

PubMed1993

Ultrastructure of plasma cells in a patient with J chain disease.

Ultrastructural analysis of plasma cells was performed in a 74-year-old female patient with J chain disease. By electron microscopy, various characteristic findings were observed: lobulated nuclei, multinuclei, single sac loop-like structures, flocculent filament-like substances, nuclear inclusion bodies, cytoplasmic inclusion bodies, and multilamellar bodies. Our prior studies pointed out a poor prognosis in myeloma patients with these findings.

Aged↗

PubMed1986

Early detection and signs of hepatoangiosarcoma among vinyl chloride workers.

Health examinations of 108 workers exposed to vinyl chloride monomer (VCM) at a Japanese chemical plant were carried out in 1979. The polymerization of vinyl chloride was started at the plant in 1949. In this study, the highest concentration of VCM in autoclaves was determined to be 250 ppm in 1961. However, the workers at the plant had been exposed to higher concentrations of VCM several times before 1960. More recent VCM exposure was considered negligible. Examinations assessed data on age, height, weight, obesity index, sake consumption, VCM exposure concentration, latent period, cumulative exposure, ICG (indocyano green test), serum bilirubin, GOT (glutamic oxaloacetic transaminase), GPT (glutamic pyruvic transaminase), A1-P (alkaline phosphatase), GGT(gamma-glutamyl transpeptidase), ZTT (zinc turbidity test), LDH (lactate dehydrogenase), cholesterol, TTT (thymol turbidity test), A/G (albumin globulin ratio), and thrombocytes. Variation in VCM exposure did not affect tests of pigment excretion from the liver, such as ICG; thrombocytes; and enzyme activity (such as GPT); nor bilirubin or flocculation reaction in serum.

Adult↗

PubMed1990

Possible heterogeneity in spondyloenchondrodysplasia: quadriparesis, basal ganglia calcifications, and chondrocyte inclusions.

We report on 6 patients with short stature and progressive enchondromatous-like changes of the vertebral bodies and the metaphyses of the long bones. Parental consanguinity was observed in 5 of 6 cases, supporting autosomal recessive inheritance. In spite of the similarity in radiographic changes and body proportions, genetic heterogeneity is suggested by the presence of CNS calcifications in 3 patients. Two of the latter had progressive quadriparesis. We tentatively classified these patients into 2 provisional types. An iliac crest biopsy in one of the patients with "type I" disease did not demonstrate enchondromatosis. Light and transmission electron microscopic studies demonstrated large cisterns and small inclusion bodies containing a flocculent material within the rough endoplasmic reticulum of the chondrocytes. Based on the histological and radiographic findings, we propose to classify these conditions among the spondylometaphyseal skeletal dysplasias.

Adolescent↗

PubMed1976

The fine structure of the interhemal membrane of the rat chorioallantoic placenta during prolonged pregnancy.

In placentas from viable rat fetuses which surgically had been retained beyond term in lactating animals for as long as four days, the fine structure of much of the interhemal membrane was quite like that of full-term placentas. Moreover, contrary to what has been reported previously (Jollie, '64a), in retained placentas which were autopsied at term there were few changes in the four cytoplasmic layers of the membrane which could be interpreted as degenerative. With prolongation of the placenta beyond normal delivery the number of pericytes which were associated with the allantoic endothelium increased; the basal lamina separating the endothelium from trophoblast III progressively became more focally split; and the apposed plasma membranes between this latter layer and trophoblast II appeared to dissociate. Trophoblast II became regionally divided in its cytoplasmic organization, its more superficial zone becoming highly infolded and/or vacuolar. As a consequence, the intertrophoblastic space between layers I and II became more extensive and complex. Within this space, a flocculent material appeared; and there was ultrastructural evidence of massive pinocytosis from the space by trophoblast II. With increased prolongation of gestation, a variety of lysosome-like inclusions appeared within this layer of the membrane.

Allantois↗

PubMed1980

Correlation of early cytodifferentiation of the human fetal prostate and Leydig cells.

The ultrastructural differentiation of the human prostatic epithelium and mesenchyme was studied in early developing glands and correlated with the differentiation of the Leydig cells of the same individuals during the tenth to sixteenth weeks. After initial folding of the basal lamina, the epithelial cells began to migrate into the differentiated, condensed mesenchyme at the end of the 10th week, and in the 11th week some of the prostatic outgrowths acquired a lumen. The acinar and tubular epithelium in the fetal prostate remained stratified, and adult type simple epithelium was not seen during the period between the 10th and 16th weeks. As a sign of incipient secretory activity, a few epithelial cells became polarized, and secretion granules with flocculent or dense content appeared in the Golgi area and in the apical parts of the cells in the 13th week. Occasional direct epithelio-mesenchymal cell contacts were visible in association with the appearance of the secretory activity. Two cell types, not seen in the normal adult prostate, appeared in the epithelium of the primitive glands. Their nature and role in the glandular morphogenesis are not clear. During this time, the ultrastructural differentiation of the Leydig cells continued and their size and number increased. They occupied almost the whole interstitium by the time secretion granules appeared in the prostatic cells. These findings support the current notion that androgens secreted by Leydig cells are the major regulators of prostatic development in man.

Cell Differentiation↗

PubMed1980

The ultrastructure of oral (buccopharyngeal) membrane formation and rupture in the chick embryo.

The ultrastructure of the oral (buccopharyngeal) membrane was examined by transmission and scanning electron microscopy (SEM) from its initial formation (stage 8) to its complete disappearance (stage 20) in the chick embryo. Thinning of the oral membrane prior to rupture occurs in large measure by increased interdigitation between cells of the stomodeal ectoderm and foregut endoderm coincident with a decrease in the width of the intervening extracellular space. Large numbers of necrotic cells were not observed. Interdigitation of ectodermal and endodermal cells makes it increasingly difficult to discern two discrete epithelia, and no evidence that one germ layer disappears prior to the other was observed. Changes occurred in the fine structure of the extracellular matrix during formation and rupture of the oral membrane, and the organization of this material within the oral membrane differed from that in regions immediately lateral to it. Copious amounts of amorphous, flocculant ("lamina-like") material are present within the oral membrane at all stages. The basal lamina of the ectoderm exhibits small loops or folds at early stages. These decrease in number as the basal lamina becomes discontinuous prior to establishment of direct intercellular contact between cells of the ectoderm and endoderm across the intervening extracellular compartment. Initial perforations of the oral membrane are preceded by clefts between cells on both sides of this structure, and SEM observations suggest that cells of the oral membrane continue to interdigitate, elongate, and change relative positions during the rupture process.

Animals↗

PubMed1981

Surface coat material associated with the cells of the developing lens vesicle in the chick embryo.

Ruthenium red (RR) and cetylpyridinium chloride (CPC) were used to demonstrate the distribution of cell surface coat material (SCM) on the free epithelial surface of the developing lens vesicle in stages 14-17 (50-64 hours) chick embryos. Observations were made by light microscopy and transmission. (TEM) and scanning (SEM) electron microscopy. A progressive increase in SCM is observed on cellular apices within the epithelium of the lens vesicle by means of RR staining, particularly at the margins of the aperture which are the sites of presumptive fusion. In contrast, a relatively thin layer of SCM persist on the adjacent surface ectoderm. Ruthenium red-positive SCM extends across the aperture of the lens vesicle prior to initial contact between the advancing epithelial surfaces. The presence of abundant SCM is interpreted as a possible significant prerequisite to invagination and to epithelial adhesion and fusion prior to detachment of the lens from surface ectoderm. When CPC is added to the fixative, a flocculent precipitate over the aperture of the lens vesicle and an associated band of modified surface ectoderm which extends ventrally from its lower margin are observed. The modified ectoderm and associated SCM likely represent a presumptive region of active coordinated cellular migration.

Animals↗

PubMed1984

Epithelial fusion during early semicircular canal formation in the embryonic zebrafish, Brachydanio rerio.

The developing inner ear of the teleost, Brachydanio rerio, provides an opportunity for observing an epithelial fusion between the apical surfaces of apposed epithelia in a vertebrate embryo in vivo. The developing otocyst was filmed for periods up to 4 days in unanesthetized embryos, and specimens were fixed at intervals and processed for light microscopy, TEM, and SEM. The semicircular canals are formed as a consequence of the union between the tips of three cylindrical projections from the wall of the otocyst, which grow toward corresponding bulges of a projection from the lateral wall. The epithelial cells covering the projections contain extensive rough endopasmic reticulum, exhibit apical junctional complexes, and are not underlain by a basal lamina. The core of each projection contains large amounts of flocculent and fibrillar extracellular material. After a period of growth and elongation, the tip of each projection contacts, and adheres to, the appropriate bulge to create a circular, flattened, bilayered, epithelial plate. Small, focal junctions form between the apposed apical cell surfaces within the plate during this period, but they are not numerous. Junctional complexes do develop, however, between apposed cells at the periphery of the plate. After 1-2 hours, the basal surface of the plate exhibit considerable alteration in contour. Adjacent cells within the plate then separate to allow continuity of the connective tissue components of the two structures. The observations of this study indicate that following an initial period of contact and adhesion, cellular reorientation and changes in junctional contacts between adjacent cells within the epithelial plate, rather than cell degeneration, are responsible for perforation of the plate.

Animals↗

PubMed1986

Morphology of norepinephrine-induced acute renal failure in the dog.

The 40-minute infusion of norepinephrine (NE) into the renal artery of dogs produces a reversible ischemic model of acute renal failure. While the physiology of this model has been extensively studied, no complete description of the pathology exists. This study uses light microscopy and transmission electron microscopy to describe and quantitate the structural and ultrastructural changes which occur in the kidneys of dogs 1, 3, and 24 hours after the intrarenal infusion of 0.75 mg/kg/minute of NE. One hour after a 40-minute NE infusion the majority of convoluted and straight proximal tubules showed apical blebs, loss of brush border, microvillar whorl formation, and mitochondrial condensation and high-amplitude swelling with flocculent densities. Necrotic cells were occasionally seen at 1 hour. The injury was progressive after 3 hours and by 24 hours animals had either complete or partial patchy necrosis of all regions of the proximal tubule. The percentages of injured and necrotic proximal tubules in outer, mid-, and inner cortical regions are presented. We conclude that the extent and pattern of injury seen after NE infusion differs significantly from the renal artery clamping model of ischemia.

Acute Kidney Injury↗

PubMed1986

Age associated increase of C cell follicles in guinea pig thyroid glands.

The effect of aging on the formation of C cell follicles was examined in the thyroid gland of guinea pigs at various ages ranging from 1 to 29 months. The C cell follicles were demonstrated with the immunoperoxidase methods by using anticalcitonin and antisomatostatin antisera and with PAS reaction. They were already detected in 1-month-old guinea pigs but in low number. Thyroid glands from 1- to 14-month-old animals contained only a small number of C cell follicles and did not reveal the age-related increase. In aged guinea pigs (20- to 29-month-old), a dramatic increase of C cell follicles was found, about 13 times as high as the number of other age groups. The C cell follicles through all age groups were present in large clusters of C cells. In the aged guinea pigs, nodular large aggregates of C cells regarded as C cell hyperplasia occurred and numerous C cell follicles were formed in the large cell aggregates. Thus, the conspicuous increase of C cell follicles in aged animals was associated with a proliferative abnormality of C cells. The C cells forming follicles showed moderate to weak immunoreactivity for calcitonin, whereas they showed very intense immunoreactivity for somatostatin. In addition, the colloidlike and flocculent materials stored in the follicular lumina, which were consistently PAS-positive, were weakly immunoreactive to somatostatin but nonreactive to calcitonin.

Aging↗