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PubMed1982

Ultrastructural abnormalities in carcinogen-induced hepatocellular altered foci identified by resistance to iron accumulation.

Hepatocellular altered foci were induced in rat liver by cycles of feeding of N-2-fluorenylacetamide and were distinguished by their resistance to iron accumulation following production of hepatic siderosis by dietary administration of 8-hydroxyquinoline and ferrous gluconate. The foci were readily identified by their iron exclusion in plastic-embedded sections stained for iron. Sections from iron-free regions processed for electron microscopy permitted ultrastructural study of cells in foci identified by reduced cytoplasmic ferritin. Altered foci of the eosinophilic type produced by cyclic feeding of carcinogen for 16 weeks were composed of both normal-appearing hepatocytes and others with ultrastructural abnormalities, including increased agranular reticulum with associated glycogen particles, decreased rough endoplasmic reticulum with reduced length of cisternae, degranulated rough vesicles, altered and displaced Golgi complexes, and abnormal bile canaliculi. At 12 and 24 weeks after cessation of carcinogen exposure, cells in persistent eosinophilic foci continued to display ultrastructural abnormalities. They possessed increased rough endoplasmic reticulum with rather regular cisternal arrangement and relatively increased smooth endoplasmic reticulum. Golgi complexes were abnormal. Bile canaliculi were abnormal and occasionally increased in number. Nuclei displayed prominent nucleoli. Cells in a basophilic focus were characterized by the presence of numerous free polyribosomes diffusely scattered throughout the cytoplasm, distended rough endoplasmic reticulum with loss of parallel-stack and hypertrophic dilated Golgi complexes, and prominent marginated nucleoli. The finding that persistent foci continued to display ultrastructural abnormalities, some of which changed or progressed in the absence of further carcinogen exposure, suggests that the persistent iron-excluding foci are a permanently altered population.

2-Acetylaminofluorene↗
PubMed1981

Ultrastructural changes in the glomerular basement membrane of patients with Laurence-Moon-Biedl-Bardet syndrome.

Renal disease, although not a cardinal feature of the Laurence-Moon-Biedl-Bardet syndrome (LMBBS), occurs in more than 70% of patients and is an important cause of morbidity and mortality. Renal ultrastructural changes have not been well delineated. We have studied glomeruli from three patients with LMBBS and have found similar ultrastructural changes in glomerular basement membrane (GBM). Two patients had decreased renal function, hypertension, and markedly abnormal intravenous urograms with reduced concentration of dye and abnormal pelvicalyceal systems; one patient had normal renal function and minimal distortion of the pelvicalyceal system of one kidney. Ligh microscopy revealed varying degrees of increase in mesangial cellularity and matrix. These changes involved almost all glomeruli and were segmental. The abnormalities ranged from mild mesangial cell proliferation to complete sclerosis of the glomerular tuft. Ultrastructural study revealed marked alterations of the glomerular basement membrane: effacement of the trilaminar architecture, segmental and irregular thickening alternating with thinning and rarefaction, accumulation of granular and fibrillary material within the inner third of the GBM. These ultrastructural changes may be the earliest and primary glomerular abnormality seen in LMBBS because they were seen in a patient who had minimal changes on light microscopy.

Adolescent↗
PubMed1981

Ultrastructure of thyroid tumors. 1. Follicular adenomas and carcinomas in rats and hamsters.

The ultrastructure of experimentally induced thyroid follicular adenomas and carcinomas was studied in rats and hamsters by means of transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Diaminobensidintetrachlorid (DAB) method was applied for cytochemical demonstration of the thyroid peroxydase activity. No significant difference was found in the ultrastructure between thyroid follicular adenomas and carcinomas in rats and hamsters. However, the ultrastructural organisation of tumor cells in carcinomas presuppose a more limited functional activity than in adenomas. The peroxydase activity of tumor cells was preserved, despite the presence of methylthiouracil (MTU) in the circulation. It was further noticed that malignant transformation of thyroid follicular cells does not lead to changes in the ultrastructural distribution of peroxydase activity. Scanning electron-microscopical examination of the thyroid tumors reveals significant changes in the structural organisation of tumor cells and follicles. The changes in the surface properties of thyroid gland in the course of malignant transformation should be considered as result of irregular cell proliferation, degenerative processes and functional heterogeneity of tumor cells.

Adenocarcinoma↗
PubMed1980

[Possibility of determination of the type of cardiomyocyte death with the aid of ultrastructural analysis].

An attempt was made to determine the ultrastructure of those types of cell death which may occur experimentally only during life and to compare them with the findings obtained from the autopsy materials of the myocardium of persons dying suddenly or from acute myocardial infarction. Three ultrastructural types of cellular death were determined in the experimental and autopsy material: primary-ischemic, primary-calcium, and secondary-calcium types. The ultrastructural pattern of some irreversible changes found in the autopsy material may be used for retrospective judgement on the mechanisms of cell death. The results obtained do not completely solve the problem of interpretation of ultrastructural findings in examinations of human postmortem materials although open some approaches for using electron microscopy in addition to the main sources of information in the study of sudden death.

Acute Disease↗
PubMed1993

Ultrastructural basis of the free-radical scavenging effect of indapamide in experimental myocardial ischemia and reperfusion.

Reperfusion of acutely ischemic cardiac tissue is associated with several characteristic pathophysiological changes that are generally referred to as "reperfusion injury." It has been hypothesized that some of these changes are mediated by oxygen-derived free radicals. Indapamide, a nonthiazide diuretic, has been shown to exert free-radical scavenging properties comparable to that of alpha-tocopherol. The purpose of the present work was to investigate whether indapamide (IDP) may limit ultrastructural signs of reperfusion injury in an experimental model of myocardial ischemia and reperfusion in isolated rat hearts. Rats received a chronic oral administration of IDP (7 days at 3 mg/kg body weight/day) before excision of the heart. IDP was also added to the perfusion fluid at a final concentration of 10(-4) M. Isolated hearts were perfused under control conditions for 20 min and then submitted to 15 min of global no-flow ischemia, before being reperfused for 15 min. Hearts were fixed by glutaraldehyde perfusion fixation and left ventricular ultrastructure was studied on ultra-thin sections by electron microscopy. Micrographs were taken following a random procedure to obtain a representative overview of the whole section. In the untreated group, marked ultrastructural alterations were observed including contraction bands, disrupted membranes, and swollen mitochondria. In the indapamide-treated group, the degree of morphological injury was significantly lessened. It is concluded that indapamide protects the ultrastructure of ventricular myocytes against reperfusion injury. This effect might be related to the oxygen free-radical scavenging property of the drug.

Animals↗
PubMed1979

Nuclear ultrastructure of epithelial cell lines derived from human carcinomas and nonmalignant tissues.

The nuclear ultrastructure of sixteen human epithelial cell lines has been characterized in detail by transmission electron microscopy. The cell lines were derived from normal tissues, nonmalignant tissues of cancerous organs, primary carcinomas, and metastatic carcinomas. Every cell section on a grid containing a clearly defined nucleus and nucleolus was scored blindly utilizing a checklist of markers. The goal of these studies was to determine whether any ultrastructural markers consistently distinguished the different stages of malignant progression represented among the lines. Nuclear bodies and perichromatin granules were found in all lines derived from cancer and were not observed in any nonmalignant lines. Nuclear envelope dilation was seen in all lines derived from cancerours organs as well as from malignant tissues but not in any lines derived from normal tissue. Margination of chromatin, irregularity of nuclear outline, redistribution of nucleolar components, and margination were expressed slightly by the normal lines, to variable degrees by the lines derived from cancerous organs, and to a much greater extent by all lines derived from malignant tissues. No differences were found between lines derived from primary carcinomas and those derived from metastatic specimens. There were no ultrastructural differences comparing subconfluent and confluent cells or cells at different passage levels. In addition, the nuclear ultrastructure of a malignant line in culture was similar to that of a tumor induced by those cells in an immunosuppressed mouse.

Cell Division↗
PubMed1993

The effects of stem cell factor on the ultrastructure of Fc epsilon RI+ cells developing in IL-3-dependent murine bone marrow-derived cell cultures.

Stem cell factor (SCF) is known to alter the proteoglycans, proteases, and cytokines synthesized by mast cells and to activate basophils. To determine whether SCF could also effect the ultrastructural characteristics of basophils and mast cells, we examined the ultrastructure of these Fc epsilon RI+ cells over 42 days in IL-3-dependent murine bone marrow-derived cell cultures in the presence or absence of SCF. Initial experiments revealed that the addition of SCF to IL-3-dependent cells enhanced their proliferative rate without influencing the percentage of Fc epsilon RI+ or metachromatic cells. We next isolated the Fc epsilon RI+ cells using flow cytometry. Light microscopy of these cells revealed mixed cultures of both immature and mature mast cells and basophils with mature mast cells predominating by 3 wk. One hundred to 150 Fc epsilon RI+ cells were then photographed by electron microscopy at 3, 10, 21, and in some cases, 42 days of culture, and the ultrastructure of each cells was evaluated by morphometry. Each cell was scored as a mast cell or basophil using standard criteria. Analysis of this data revealed that SCF in the presence of IL-3 promoted the development of mast cells, although a significant number of basophils were noted at day 21 but were absent by day 42. When bone marrow cells cultured in IL-3 + SCF were compared with cells cultured in IL-3 alone, a significant decrease in cell and nuclear size and granule number and size was noted in both mast cells and basophils cultured in IL-3 + SCF, and basophils and mast cells under these conditions most resemble their in vivo counterparts. Thus, SCF in the presence of IL-3 increases the ratio of mast cells to basophils and alters the ultrastructural characteristics of mast cells and basophils toward a more mature phenotype.

Animals↗
PubMed1994

[Rat model of HTLV-I infection--ultrastructural study of HAM rat disease].

HAM (HTLV-I-associated myelopathy) rat disease, HAM/TSP (HTLV-I-associated myelopathy/tropical spastic paraparesis)-like myelopathy in rats, occurred in 8 of 8 HTLV-I (Human T cell leukemia virus type I) carrier rats of WKAH strain inoculated with MT-2 cells at either neonates or 4 to 6 months of age. We report here ultrastructural findings of the affected spinal cords and the peripheral nerves of perfusion-fixed HAM rats. They were infected at the age of 4 to 6 months old and showed gait disturbance and hind leg paraparesis 15 months after infection. Pathological alterations of HAM rat disease were mainly confined to marginal areas of white matter of the spinal cord. The affected lesion was rather symmetrical and distributed in the anterior and the lateral columns. A prominent ultrastructural change in the spinal cord was separation of myelin lamellae at the intraperiod line and vacuolation of myelin sheath. Many myelin-debris-filled macrophages and a marked astrogliosis were also observed. In the gliotic areas, lots of demyelinated and remyelinated axons were intermingled. Axons were relatively preserved, however, some of them had tubulo-reticular inclusions. Astrocytes appeared ultrastructurally normal. Lymphocytic infiltration was virtually absent. Ultrastructural alterations of the peripheral nerve were basically similar to those of the spinal cord. Separation of myelin lamellae, macrophages infiltration, demyelination, and remyelination were observed. Schwann cells had also alterations. We observed some apoptotic cell death of the oligodendrocytes and Schwann cells with condensed nucleus and phagocytosis of apoptotic bodies by macrophages. Collective evidence suggests that a series of demyelinating process described above may be caused by apoptosis. No virus particles were seen in the spinal cord and peripheral nerve. Although the precise mechanism of apoptosis is not known at present, possible pathogenetic pathway involving apoptosis in HAM rat disease may contribute greatly to a better understanding of mechanisms implicated in the pathogenesis of HAM/TSP in humans.

Animals↗
PubMedDate not supplied

[Use of freeze-fracturing to observe the ultrastructure of Candida albicans with scanning electron microscopy].

The development of the techniques of sample preparation for the observation of ultrastructure with scanning electron microscopy (SEM) include, among others, the method O-D-O reported by Tanaka and Naguro in 1981, based on the initial fixing of the specimen (eukaryotic tissue) in 1% OsO4; treatment with dimethyl sulphoxide (DMSO) as a cryoprotectant, followed by cryofracture, removal of cytoplasmatic matrix by psot-fixing with 1% OsO4 and a further conductive stain. In this paper we report the application of the method O-D-O in a culture of Candida albicans modifying the pre-fixing carried out overnight and excepting the osmic maceration, in order to observe the cell ultrastructure of this eukaryotic microorganism with SEM at a normal resolution. Through the tridimensional images obtained, in which we can observe the fracture of Candida albicans without cytoplasmatic matrix but with details of a normal and deformed cell wall, as well as cells conserving their cytoplasmatic matrix where globose and filamentous structures become evident and suggest a pattern of organization and cells with a very clear character of what we believe is the nuclear zone of the microorganism, we night conclude that our method is suitable for eukaryotic unicellular organisms in order to observe the cell ultrastructure with SEM at normal resolution and show images comparable with those reported with SEM at high resolution, contributing to the development of the ultrastructural cytology, traditionally restricted to the transmission electron microscopy (TEM). These findings reveal an additional aid which will allow to obtain a clearer aspect of the complex cell structure of unicellular organisms.

Candida albicans↗
PubMed1994

Ultrastructural changes in mild gastroesophageal reflux disease: results of a pilot study.

Few studies have examined the ultrastructural changes in mild reflux esophagitis. Endoscopic esophageal biopsies were obtained from 10 patients with reflux symptoms and mild endoscopic esophagitis (grade 0:3 patients, grade I: 7 patients) and 9 patients with erosive esophagitis (grade II-IV), at least 5 cm above the Z line. The biopsies were evaluated by light and transmission electron microscopy. Ultrastructural changes were present in one patient with grade 0, 7 with grade I and 9 with grade II-IV esophagitis. Four of the 10 patients with grade 0-I esophagitis and 6 of 9 with grade II-IV esophagitis had light microscopic abnormalities. The ultrastructural abnormalities in patients with mild esophagitis were seen in the cell membrane, cytoplasmic organelles, desmosomes, and nuclei of all the three layers of esophageal mucosa and the basal lamina. Ultrastructural studies by transmission electron microscopy on endoscopic pinch biopsies may be a sensitive research tool to study the pathogenesis of mild reflux esophagitis.

Adult↗
PubMedDate not supplied

Hepatic and renal ultrastructural changes in cockerels exposed to cadmium chloride and subsequent interaction with organophosphate insecticide.

Ultrastructural alterations of the liver and kidneys of cockerels exposed to 100 ppm of cadmium chloride (CdCl2) and subsequent interaction with an organophosphorus compound (methylobromofenvinphos) were studied. Four groups, each consisting of 25 birds, included 100 ppm of CdCl2 in drinking water for 4 weeks (Group A), 100 ppm of CdCl2 for 4 weeks followed by a single dose of 240 mg/kg of methylobromofenvinphos (IPO 63 compound) (Group B), single dose of 240 mg/kg of IPO 63 compound (Group C), and untreated control (Group D). Three birds from each group were sacrificed 24 hr post treatment with IPO 63 compound and tissue pieces were collected for electron microscopic study. Ultrastructural changes in hepatocytes included swollen mitochondria with cavitation, dilated rough endoplasmic reticulum, numerous lysosomal bodies, myelin figures, depletion of glycogen granules, and numerous vacuoles containing degenerated membranes in birds that interacted with CdCl2. In a few cells the nuclei were markedly damaged with dilation of envelope. Renal corpuscles of CdCl2 showed irregular foot processes and thickening of the glomerular basement membrane. The proximal tubular cells of CdCl2 birds showed marked ultrastructural alterations, including numerous lysosomal bodies, few fat droplets, membrane bound vacuoles studded with polyribosomes, swollen mitochondria with fragmented cristae surrounded by rough endoplasmic reticulum, vacuoles containing myelin figures, and damaged nuclei with dilated envelope. Minor ultrastructural alterations were observed in the liver and kidneys of birds treated with cadmium alone and of those treated only with IPO 63 compound. These observations suggest that treatment with CdCl2 and then subsequent interaction with IPO 63 compound causes hepatic and renal damage that appears to be additive.

Animals↗
PubMed1993

Ultrastructural characteristics of Fc epsilon R-positive basophils in the spleen and bone marrow of mice immunized with goat anti-mouse IgD antibody.

BACKGROUND: Previous work showed that injection of mice with goat anti-mouse IgD antibodies results in increased numbers of Fc epsilon R-positive, non-B, non-T cells in the spleen and Fc epsilon R-positive cells in the bone marrow, and that some of these cells had ultrastructural features of basophils. Fc epsilon R-positive, non-B, non-T cells express virtually all of the capacity of mouse splenic "non-B, non-T cells" to produce interleukin-4 in response to stimulation by cross-linking of Fc epsilon R or Fc gamma R, or by the calcium ionophore, ionomycin. EXPERIMENTAL DESIGN: The present study is a detailed ultrastructural analysis of Fc epsilon R-positive bone marrow cells or Fc epsilon R-positive splenic non-B, non-T cells sorted from mice injected with goat anti-mouse IgD antibody and of Fc epsilon R-positive bone marrow cells or spleen cells pooled from normal mice not injected with goat anti-IgD. RESULTS: Basophils represented the majority (90%) of the granulated cells present in the Fc epsilon R-positive splenic non-B, non-T cells or Fc epsilon R-positive bone marrow cells of goat anti-IgD-injected mice. In contrast, the cytoplasmic granule-containing Fc epsilon R-negative cells sorted from spleen or bone marrow of goat anti-IgD-injected animals contained predominantly a mixture of neutrophils, eosinophils, monocytes and their precursors. Both the Fc epsilon R-positive and -negative preparations contained rare (< 5%) cells with ultrastructural features of very immature mast cells. Basophils were also identified in Fc epsilon R-positive cells sorted from total bone marrow cells or spleen cells of normal mice not injected with goat anti-IgD. CONCLUSIONS: Taken together with data concerning the numbers of Fc epsilon R-positive, non-B, non-T cells in the spleen, and Fc epsilon R-positive B220-negative cells in the bone marrow, these ultrastructural findings indicate that injection of mice with goat anti-IgD results in increased numbers of basophils, particularly in the spleen, that exhibit an 8-fold increase in basophils as a result of injection of goat anti-IgD.

Animals↗
PubMed1996

A high resolution ultrastructural study of experimental murine AA amyloid.

An essential and distinguishing feature of all amyloids is the presence of fibrillar structures of approximately 10-nm width. The precise nature of the fibril is not yet clearly understood, particularly in situ, and the ultrastructure of isolated fibrils differs significantly from that of fibrils observed in situ. The fibrils are generally believed to be composed of a protein specific to each type of amyloid, but increasing evidence suggests additional associations with other components such as heparan sulfate proteoglycan (HSPG) and amyloid P component (AP). Experimental AA amyloidosis was induced in mice by amyloid enhancing factor and an inflammatory stimulus (subcutaneous AgNO3); fibrils were thereafter examined in detail. Particular attention was paid to ultrastructural characteristics known to represent particular molecular components of basement membranes such as HSPG and AP. Additionally, rabbit anti-mouse AA antisera was used with 5-nm and 1-nm gold particles to establish the location of the AA protein in-situ. Amyloid fibrils could be identified in their mature form as well as at apparent intermediate stages of formation. The fibril contained an apparent core which is composed of an assembly of 3.5-nm wide pentosomal particles having the characteristics of AP. Wound around the AP assembly in a helical fashion is a "double tracked" ribbon-like entity, 3 nm wide, having the morphologic characteristics of chondroitin sulfate proteoglycan (CSPG). Covering the surface of this structure is a second ribbon-like double track structure, but this one is wider (4.6 nm vs 3.0 nm) than the CSPG. These have the ultrastructural characteristics of HSPG. Routine fixation and tissue preparation techniques that usually remove HSPG from microfibrils did not do so with amyloid fibrils, suggesting an alteration in affinity between these components. The AA protein could be identified as a 1 - to 2-nm filament network on the most exterior surface of the fibril. The ultrastructure of AA amyloid fibrils in situ resembles that of connective tissue microfibrils, and, in addition to AA protein, is likely composed of HSPG, CSPG, and AP. Amyloid fibrils can be distinguished from microfibrils by the apparently stronger binding of HSPG to the surface of the amyloid fibril and the presence of the AA filaments. A model of the in situ organization of AA amyloid fibrils is proposed.

Amyloidosis↗
PubMed1996

Ultrastructural instability of paired helical filaments from corticobasal degeneration as examined by scanning transmission electron microscopy.

Paired helical filaments (PHFs) accumulate in the brains of subjects affected with Alzheimer's disease (AD) and certain other neurodegenerative disorders, including corticobasal degeneration (CBD). Electron microscope studies have shown that PHFs from CBD differ from those of AD by being wider and having a longer periodicity of the helical twist. Moreover, PHFs from CBD have been shown to be primarily composed of two rather than three highly phosphorylated polypeptides of tau (PHF-tau), with these polypeptides expressing no exons 3 and 10. To further explore the relationship between the heterogeneity of PHF-tau and the appearance of abnormal filaments, the ultrastructure and physical parameters such as mass per unit length and dimensions were compared in filaments from CBD and AD using high resolution scanning transmission electron microscopy (STEM). Filament-enriched fractions were isolated as Sarcosyl-insoluble pellets and for STEM studies, samples were freeze-dried without prior fixation or staining. Ultrastructurally, PHFs from CBD were shown to be a heterogeneous population as double- and single-stranded filaments could be identified based on their width and physical mass per unit length expressed in kilodaltons (kd) per nanometer (nm). Less abundant, double-stranded filaments had a maximal width of 29 nm and a mass per unit length of 133 kd/nm, whereas three times more abundant single-stranded filaments were 15 nm wide and bad a mass per unit length of 62 kd/nm. Double-stranded filaments also displayed a distinct axial region of less dense mass, which appeared to divide the PHFs into two protofilament-like strands. Furthermore, these filaments were frequently observed to physically separate along the long axis into two single strands or to break longitudinally. In contrast, PHFs from AD were ultrastructurally stable and uniform both in their width (22 nm) and physical mass per unit length (104 kd/nm). The ultrastructural features indicate that filaments of CBD and AD differ both in stability and packing of tau and that CBD filaments, composed of two distinct protofilaments, are more labile under STEM conditions. As fixed and stained filaments from CBD have been shown to be stable and uniform in size by conventional transmission electron microscopy, STEM studies may be particularly suitable for detecting instability of unstained and unfixed filaments. The results also suggest that molecular heterogeneity and/or post-translational modifications of tau may strongly influence the morphology and stability of abnormal filaments.

Aged↗
PubMed1996

Ultrastructural and immunohistochemical studies of stromal cells in lamina propria of human fallopian tube ampullar mucosa: the recognition of 'CD34 positive reticular network' and its putative function for immune surveillance.

This paper aims at clarifying the cellular differentiation at the ultrastructural and immunohistochemical levels in normal stromal cells of the fallopian tube ampullar mucosa in order to arrive at a functional interpretation of these cells. Techniques used were histology, histochemistry, transmission and scanning electron microscopy, as well as light and ultrastructural immunohistochemistry for the CD34 antigen. Three types of stromal mesenchymal cell were identified. The most frequent cell-type had a fibroblastic shape and lacked the lamina and myofilaments typical of smooth-muscle. It was, however, positive for alpha-smooth-muscle actin (alpha-SMA). It was negative for desmin (D), but positive for the CD34 antigen. This cell was therefore rather undifferentiated ultrastructurally but had a partial smooth-muscle immunophenotype: it was designated as an ultrastructurally undifferentiated smooth-muscle cell (U-SM cell). A second category consisted of overt smooth-muscle cells (SM cells): they were rich in myofilaments, had a lamina and were D(+) and alpha-SMA(+). The third category resembled SM cells but were D(-): these were designated D(-) SM cells. U-SM cells, SM cells and D(-)SM cells accounted for 83%, 13% and 4% of the total stromal cell population respectively. U-SM cells had lipid-rich residual bodies, solitary cilia, simple intercellular and cell-to-matrix junction, and they were frequently adherent to mononuclear cells. This phenotype was present irrespective of the varied clinical picture of the patients from whom samples were obtained. The observations suggest that the stroma of the fallopian tube ampullar mucosa consists of a reticulum composed largely of CD34(+) U-SM cells in combination with mononuclear cells. One of the main roles suggested for this CD34 positive reticular network is immune surveillance.

Acid Phosphatase↗
PubMed1996

Ultrastructural demonstration of apoptosis, Fas and Bcl-2 expression of rheumatoid synovial fibroblasts.

OBJECTIVE: There is evidence that proliferation of synovial fibroblasts and invasive growth in rheumatoid arthritis (RA) is due to impaired regulation of the cell cycle, i.e., the balance between proliferation and physiological cell death (apoptosis) We examined synovial tissues from patients with RA and osteoarthritis (OA) to determine the ultrastructural changes during apoptosis and the expression of the apoptosis regulating molecules Fas and Bcl-2 in synovial fibroblasts. METHODS: We examined synovial tissues obtained from patients with RA and OA by electron microscopy and immunoelectron microscopy to evaluate the characteristics of apoptosis in RA synovial fibroblasts as well as Fas and Bcl-2 antigen expression. RESULTS: Ultrastructurally, the majority of the RA synovial fibroblasts appeared transformed, and 3% of these were in different stages of apoptosis. In OA, no apoptotic cells could be observed. Apoptosis of synovial fibroblasts in RA showed a characteristic multistage pattern. In each of the distinguishable 4 stages, specific ultrastructural changes could be detected. The apoptotic synovial fibroblasts were mainly located in the deeper sublining layers of the synovium. Immunoelectron microscopy revealed that Fas antigen expression was limited to the first stage of apoptosis. Conversely, the synovial fibroblasts located in the synovial lining layer neither underwent apoptosis nor expressed Fas antigen. Several synovial lining cells expressed the cell death suppressor (anti-apoptosis) gene product Bcl-2. CONCLUSION: Apoptosis of fibroblasts in the RA synovial sublining is characterized by a distinct multistep ultrastructural pattern with a detectable initial Fas antigen expression; conversely, reduced apoptosis in the synovial lining associated with the expression of Bcl-2 results in extended life of matrix degrading synovial fibroblasts at the site of synovial invasion into cartilage and bone.

Adult↗
PubMed1996

Ultrastructural abnormalities in the dermal papillae of both lesional and clinically normal follicles from alopecia areata scalps.

Alopecia areata is a form of balding whose aetiology is uncertain. Although the dermal papilla in the hair bulb regulates the follicle and may play a part in the pathogenesis of alopecia areata, its ultrastructure has not been well described. As clinically normal, i.e. non-balding, follicles from alopecia areata scalps show abnormalities at the light microscope level, it would be expected that they should exhibit the earliest pathological changes involved in the dysfunction of the follicle. This study was designed to investigate the ultrastructure of normal human scalp follicular dermal papillae and to see if changes occurred in the ultrastructure of dermal papillae from either lesional or non-balding regions of alopecia areata. Normal dermal papillae contained well formed fibroblast-like cells with large, oval nuclei and well-developed endoplasmic reticulum; the cells were separated from each other by extracellular matrix containing small pieces of collagen and basal lamina-like material. Dermal papillae from both clinically normal and lesional alopecia areata follicles were less well organized and the dermal papilla cells exhibited signs of cell injury and contained abnormal amounts of pigment; an increased concentration of fibrous material in the extracellular matrix and thickening of the dermal papilla-epithelial junction were also seen. Follicles from lesional areas showed more pronounced changes than clinically normal ones. Ultrastructural abnormalities in the dermal papillae of clinically normal scalp follicles support the study of these follicles as a prime research target. The changes detected suggest that dermal papilla cells in alopecia areata would be less able to synthesize regulatory factors and that these may have more difficulty crossing into the epithelial compartment. They are consistent with an early pathological role for the dermal papilla in alopecia areata, but do not distinguish whether this is a primary aetiological role or a secondary response to an insult elsewhere in the follicle.

Adolescent↗
PubMed1996

A comparison of the ultrastructure of perfusion-deficient and functional lung parenchyma in CBA mice during the late phase after irradiation.

The ultrastructure of lung parenchyma of CBA/J mice 1 year after 14 Gy X irradiation was studied by transmission electron microscopy (TEM) and compared with the ultrastructure of age-matched control mice. The irradiated mice had received an injection of colloidal carbon just prior to death to identify patent capillaries. Regions containing carbon were compared by TEM with apparently nonperfused areas lacking carbon. The interalveolar interstitial tissue and the capillary endothelium were not different ultrastructurally in perfused and nonperfused regions. There were no appreciable differences between irradiated and unirradiated lung, except for small, infrequent focal areas with a slight increase in the number of collagen fibers. The ultrastructural examination did not reveal any lesion which might have been missed in the preliminary light microscope studies, which confirms that the lack of perfusion in CBA/J mice which have an appreciable respiratory functional deficit in the late phase is not due to the loss of patent capillaries or to fibrosis of the alveolar wall. It was concluded that the lesion must be at the "pre-capillary" level, probably damage to or loss of small blood vessels.

Animals↗