Amorphous Electron-dense Material Research Articles

Histological, immunohistochemical and ultrastructural features of polyglucosan bodies in uterine smooth muscle of pet rabbits (Oryctolaguscuniculus)

We document the frequency and morphological and immunohistochemical features of inclusion bodies in uterine smooth muscle cells in 56 (76%) of 74 investigated pet rabbits (Oryctolagus cuniculus). Inclusion bodies began to appear at the age of 2 years and their frequency increased with age (P = 0.047, r = 0.33). They ranged from 5 to 20 μm in diameter, were slightly basophilic to amphophilic with well-delimited oval bodies in haematoxylin and eosin-stained tissue sections and formed in the cytoplasm of the uterine smooth muscle cells with displacement of the cell nuclei. The inclusion bodies were positive with periodic acid–Schiff, Best's carmine, Lugol's iodine and Grocott's methenamine silver methods. They were immunoreactive to a monoclonal antibody raised against human polyglucosan and negative with monoclonal antibodies for several intermediate filament proteins. Electron microscopy revealed that they were non-membranous structures composed of electron-dense amorphous material. The morphological, histochemical, immunohistochemical and ultrastructural features of the inclusion bodies in the rabbi uteri were similar to those of human polyglucosan bodies (PGBs). PGBs appear to occur at a high frequency in the uterus of rabbits, which are known to be susceptible to uterine diseases.

Pathomorphological changes of capillaries in the cerebral cortex in type 2 diabetes mellitus

The aim of the study was to determine microscopic, immunohistochemical, electron microscopic, morphometric parameters of capillaries in the cerebral cortex in deceased patients with type 2 diabetes mellitus (DM) in comparison with the conditional control group and the group of deceased patients with dyscirculatory ischemic encephalopathy. Materials and methods. Microscopic, immunohistochemical, electron microscopic and morphometric studies of the cerebral cortex capillaries were performed in 3 groups: group I – 20 deceased patients with type 2 DM, group II conditional control (CC) – 20 deceased patients without clinical morphological signs of DM and cerebrovascular pathology, group III – 20 patients with dyscirculatory ischemic encephalopathy (DIEP). Results. It was found that in type 2 DM, the capillaries in the cerebral cortex lose pericytes due to their apoptosis: the number of pericytes in the cortical capillaries in type 2 DM was statistically significantly lower by 57.14 % compared to CC group and 50.00 % lower compared to DIEP group, the level of caspase-3 expression in the cortical microvessels in type 2 DM was significantly higher by 230.85 % compared with CC group and 81.67 % higher than in DIEP group. According to electron microscopy in type 2 DM, apoptosis of pericytes and single endothelial cells in the cerebral cortex capillaries was determined as well as significant expansion of basement membranes with the accumulation of electron-dense amorphous material and collagen fibrils. According to the results of morphometry, the outer diameter of the cortical capillaries in type 2 DM group was 4.90 % significantly larger, the inner diameter was 9.78 % smaller and the walls were 66.62 % thicker (compared with CC group) due to the accumulation of PAS-positive substances of blood serum and fibrosis, confirmed by 22.96 % greater area of type IV collagen expression in the microvessel walls. Conclusions. The pathomorphological changes of microvessels identified in deceased patients with type 2 diabetes mellitus are signs of diabetic cerebral microangiopathy.

Structural associations between organelle membranes in nectary parenchyma cells.

The close association between membranes and organelles, and the intense chloroplast remodeling in parenchyma cells of extrafloral nectaries occurred only at the secretion time and suggest a relationship with the nectar secretion. Associations between membranes and organelles have been well documented in different tissues and cells of plants, but poorly explored in secretory cells. Here, we described the close physical juxtaposition between membranes and organelles, mainly with chloroplasts, in parenchyma cells of Citharexylum myrianthum (Verbenaeceae) extrafloral nectaries under transmission electron microscopy, using conventional and microwave fixation. At the time of nectar secretion, nectary parenchyma cells exhibit a multitude of different organelle and membrane associations as mitochondria-mitochondria, mitochondria-endoplasmic reticulum, mitochondria-chloroplast, chloroplast-nuclear envelope, mitochondria-nuclear envelope, chloroplast-plasmalemma, chloroplast-chloroplast, chloroplast-tonoplast, chloroplast-peroxisome, and mitochondria-peroxisome. These associations were visualized as amorphous electron-dense material, a network of dense fibrillar material and/or dense bridges. Chloroplasts exhibited protrusions variable in shape and extension, which bring them closer to each other and to plasmalemma, tonoplast, and nuclear envelope. Parenchyma cells in the pre- and post-secretory stages did not exhibit any association or juxtaposition of membranes and organelles, and chloroplast protrusions were absent. Chloroplasts had peripheral reticulum that was more developed in the secretory stage. We propose that such subcellular phenomena during the time of nectar secretion optimize the movement of signaling molecules and the exchange of metabolites. Our results open new avenues on the potential mechanisms of organelle contact in parenchyma nectary cells, and reveal new attributes of the secretory cells on the subcellular level.

Ultrastructural changes of epidermal calcium gradient and lipid lamellar membrane in depigmented skin lesions of vitiligo patients

To investigate the effects of melanin disappearance in vitiliginous skin on the ultrastructure of epidermal calcium distribution and the stratum corneum (SC) lipid lamellar membranes. Five outpatients with stable vitiligo vulgaris and 5 healthy controls were recruited from August 2014 to February 2015 at Department of Dermatology, Renmin Hospital of Wuhan University. The ultrastructural changes of lipid lamellar membranes of the skin were assessed using transmission electron microscopy (TEM) technique in combination with ruthenium tetroxide (RuO4) staining. The concentration and distribution of calcium precipitates in the epidermis were studied using calcium ion-capture cytochemistry combined with TEM. The multilayered lipid lamellae existed within the intercellular space of the normal SC with a characteristic alternating electron-dense and electron-lucent pattern. Expanded intercellular space, fragmentation and lamellar separation were observed in the depigmented skin lesions from vitiligo patients, the bulbous regions of lipid lamellae were filled with electron-dense amorphous materials. Large clumps of calcium precipitates were visualized in the stratum granulosum (SG) of normal skin, fine calcium precipitates and stage Ⅳ melanosomes were noted within the normal stratum basale (SB). In depigmented skin lesions of vitiligo, both the size and number of calcium precipitates in the SG were dramatically decreased. Melanosome was barely seen in the vitiligo SB. Disrupted ultrastructure of SC lamellar membranes and disappearance of calcium gradient co-exist in the skin lesion of vitiligo, indicating that melanin in epidermis may play a role in formation of epidermal calcium gradient and maintenance of structural integrity of permeability barrier.

Ultrastructural immunolocalization of chatelicidin-like peptides in granulocytes of normal and regenerating lizard tissues

The presence and localization of cathelicidin anti-microbial peptides in the lizard, Anolis carolinensis, were investigated by immunocytochemistry. The study showed that immunoreactivity for cathelicidins 1 and 2 was only present in large granules of heterophilic–basophilic granulocytes, rarely found in the dermis and sub-dermal muscle in normal and more frequently in wound and regenerating skin tissues or in the blood. Some immunopositive granulocytes were also observed among the keratinocytes of the wound epithelium covering the tail stump and occasionally in the regenerating epidermis of the tail. Immunolabeling for cathelicidins was also seen in low electrondense amorphous material present on the surface of the wound epidermis and on the plasma membrane of bacteria present on the surface of corneocytes of the epidermis. Immunolabeling for cathelicidins was absent in the other cell types and in control sections. The study suggests that cathelicidins are normally stored in granulocytes in the blood or in connective tissues, while keratinocytes can be stimulated to produce and possibly release these molecules only after injury or microbial invasion.

Dermoscopic and Reflectance Confocal Microscopic Features of Exogenous Ochronosis

Exogenous ochronosis presents as an acquired asymptomatic hyperpigmentation on photoexposed areas, predominantly over bony prominences, and is caused by the topical application of several skin-lightening agents. We describe a 63-year-old Hispanic woman who developed exogenous ochronosis lesions on her face after using topical bleaching creams containing hydroquinone, 2% to 3%, and oxybenzone, 2%, for several years. Dermoscopy revealed irregular brown-gray globular, annular, and arciform structures that corresponded to focal deposition of ochronotic pigment on the dermis. These deposits correlated with multiple banana-shaped nonrefractile structures seen using reflectance confocal microscopy. Histopathologic sections revealed the deposition of a banana-shaped, yellow to brown material in the papillary and middle dermis. Ultrastructural examination revealed an amorphous electron-dense material mostly located in the core of elastic fibers and also in smaller amounts in the interstitium with prominent degenerative changes in the elastic fibers. A good correlation was observed between the results of both noninvasive techniques and the diagnostic histologic features of this condition. We characterized by means of dermoscopy, reflectance confocal microscopy, and electronic microscopy a case of exogenous ochronosis. To our knowledge, this is the first description of reflectance confocal microscopic findings in this condition. Dermoscopy and reflectance confocal microscopy are proved to be useful noninvasive techniques for the diagnosis of this pigmentary disorder.

Pollen tube reuses intracellular components of nucellar cells undergoing programmed cell death in Pinus densiflora

Through the process known as programmed cell death (PCD), nucelli of Pinus densiflora serve as the transmitting tissue for growth of the pollen tube. We sought to clarify the processes of degradation of nucellar cell components and their transport to the pollen tube during PCD in response to pollen tube penetration of such nucelli. Stimulated by pollination, synthesis of large amounts of starch grains occurred in cells in a wide region of the nucellus, but as the pollen tube penetrated the nucellus, starch grains were degraded in amyloplasts of nucellar cells. In cells undergoing PCD, electron-dense vacuoles with high membrane contrast appeared, assumed a variety of autophagic structures, expanded, and ultimately collapsed and disappeared. Vesicles and electron-dense amorphous materials were released inside the thickened walls of cells undergoing PCD, and those vesicles and materials reaching the pollen tube after passing through the extracellular matrix were taken into the tube by endocytosis. These results show that in PCD of nucellar cells, intracellular materials are degraded in amyloplasts and vacuoles, and some of the degraded material is supplied to the pollen tube by vesicular transport to support tube growth.

Annual Meeting of the Society for Cutaneous Ultrastructure Research (34th Annual Meeting of SCUR)

Kindler syndrome is an autosomal recessive genodermatosis characterized by trauma-induced acral skin blistering from infancy, photosensitivity, generalized poikiloderma, and diffuse cutaneous atrophy. Mutations in the KIND1 gene that encodes for the focal contact-associated protein kindlin-1 have been identified in several patients although the spectrum of clinical abnormalities is protean and genetic heterogeneity is plausible. A 32-year-old Japanese male, born to consanguineous parents, presented with acral skin blistering, cutaneous atrophy, palmoplantar thickening, finger contractures, absence of dermatoglyphics, and nail dystrophy. He also had leukoplakia of the tongue but did not report photosensitivity or show signs of poikiloderma. A biopsy taken from bullous atrophic skin on the dorsal surface of his left hand showed sub-epidermal blistering, vacuoles within basal keratinocytes and immunohistochemical evidence of basement membrane reduplication. Intensity of Kindlin-1 expression in patient skin was indistinguishable from that in normal skin. Electron microscopy demonstrated multiple tubulo-vesicular structures and electron dense amorphous keratinocyte-derived material immediately below the dermal-epidermal junction. Mutational analysis of the KIND1 gene failed to identify any pathogenic mutation(s). Although this patient’s clinical and skin biopsy features appear to match the clinico-pathological criteria for a diagnosis of Kindler syndrome, no mutation in KIND1 was detected. This suggests genetic heterogeneity in this genodermatosis or perhaps the existence of a subset of patients that have a distinct but currently unclassified related inherited disorder. Identification of similar patients and characterization of this Kindler-like syndrome is expected to provide new insight into clinical disorders associated with structural pathology within the cutaneous basement membrane zone.

Bunina bodies in amyotrophic lateral sclerosis

Bunina bodies, which are small eosinophilic intraneuronal inclusions in the remaining lower motor neurons, are generally considered to be a specific pathologic hallmark of amyotrophic lateral sclerosis (ALS). One year before a publication by Bunina, van Reeth et al. described similar intracytoplasmic inclusions in the anterior horn cells in a patient with Pick's dementia with atypical ALS. At present, only two proteins have been shown to be present in Bunina bodies, one is cystatin C and the other is transferrin. Bunina bodies consist of amorphous electron-dense material surrounded by tubular and vesicular structures on electron microscopy. Although the nature and significance of Bunina bodies in ALS are not yet clear, the bodies may be abnormal accumulations of unknown proteinous materials.

Light chain deposition disease restricted to the brain: the first case report

A 35-year-old white male with symptoms of paranoid schizophrenia was treated by psychiatrists for 13 years. During the final year, he developed severe dysphagia, reduced strength of the upper extremity muscles, and cognitive dysfunction. The patient died in his sleep. The only pathology found in coronal brain sections was ill-defined periventricular foci with prominent, firm vessels. Microscopy revealed abundant, hematoxylin and eosin-eosinophilic, periodic acid-Schiff-positive, thioflavin T-positive, and Congo red-negative deposits in the vessel walls, with hypoxic encephalopathy in the affected regions. Immunohistochemistry showed lambda light chains as the main component of the deposits. Ultrastructural analysis showed amorphous electron dense material in the vessel walls. Perivascular B-cell proliferation was present in the vicinity of affected areas. Polymerase chain reaction was applied for the assessment of B-cell clonality, revealing monoclonal rearrangement of the heavy chain Ig gene. Neither in the kidney nor in any other organ were deposits detected. This is the first case report of light chain deposition disease restricted to the brain.

Colony development in Streptomyces carpinensis: a streptomycete with substrate mycelium spores

In this paper we present an ultrastructural study of spore formation in aerial vs. substrate mycelia of Streptomyces carpinensis. Both mycelia initiated spore formation at nearly the same time of colony development but exhibited different patterns of spatial localization of sporulation: spore formation took place throughout the aerial mycelium whereas in the substrate mycelium was confined to a narrow zone at the bottom of the colony. The ultrastructural changes leading to spore formation, however, were quite similar in both mycelia, differing only with respect to the outer components of the sporal wall. Spores formed in the aerial mycelium were covered by a thin sheath whereas the spores formed in the substrate mycelium were covered by an amorphous electron-dense material.

Ultrastructure of maize necrotic streak virus infections.

Maize necrotic streak virus (MNeSV) has 32 nm isometric particles that encapsidate a single stranded RNA genome ca. 4.3 kb in size, and is a tentative member of the genus Tombusvirus. Since tombusviruses elicit the formation of cytopathological structures known as “multivesicular bodies” that assist in their classification at the genus level, the cytology of thin-sectioned maize leaf tissues 7, 15, and 45 days after inoculation was investigated. The prominent cytopathological features were: (i) an extensive accumulation of virus particles scattered throughout the cytoplasm or in crystalline arrays in the cytoplasm or, occasionally, in intercellular spaces; (ii) extensive plasmolysis and the appearance of small patches of amorphous, dark-staining material in the cytoplasm; (iii) the proliferation of membranes and the presence of empty double membrane-bound vesicular structures of various sizes. No apparent connection between these membranous elements and the nuclear envelope was detected, even when large clusters of vesicles were adpressed to the nuclei. Some of the largest double-membrane bound structures had rows of small vesicles located inside peripheral dilations of the bounding membrane. Although most of these structures appeared to originate from disintegrating mitochondria, they bore little resemblance to genuine multivesicular bodies like those arising from the modified mitochondria that follow infection by certain members of the family Tombusviridae, i.e. Carnation Italian ringspot virus, Pelargonium necrotic spot virus (PNSV), Galinsoga mosaic virus (GaMV), and Turnip crinkle virus (TCV). Immunogold labelling using antibodies to virus particles was detected over cytoplasm associated with virus particles and patches of electrondense amorphous material, suggesting that this material consists of virus coat protein.

Unstable microtubule capture at kinetochores depleted of the centromere-associated protein CENP-F

Centromere protein F (CENP-F) (or mitosin) accumulates to become an abundant nuclear protein in G2, assembles at kinetochores in late G2, remains kinetochore-bound until anaphase, and is degraded at the end of mitosis. Here we show that the absence of nuclear CENP-F does not affect cell cycle progression in S and G2. In a subset of CENP-F depleted cells, kinetochore assembly fails completely, thereby provoking massive chromosome mis-segregation. In contrast, the majority of CENP-F depleted cells exhibit a strong mitotic delay with reduced tension between kinetochores of aligned, bi-oriented sister chromatids and decreased stability of kinetochore microtubules. These latter kinetochores generate mitotic checkpoint signaling when unattached, recruiting maximum levels of Mad2. Use of YFP-marked Mad1 reveals that throughout the mitotic delay some aligned, CENP-F depleted kinetochores continuously recruit Mad1. Others rebind YFP-Mad1 intermittently so as to produce 'twinkling', demonstrating cycles of mitotic checkpoint reactivation and silencing and a crucial role for CENP-F in efficient assembly of a stable microtubule-kinetochore interface.

Occurrence of hyaline droplets in renal biopsy specimens: an ultrastructural study

Hyaline droplets are apical cytoplasmic vesicles containing an accumulation of electron-dense amorphous materials surrounded by a unit membrane. Hyaline droplets may originate from apical vesicles after conversion to osmotic vesicles and loss of internally lined glycocalyx. They are found in the proximal tubular epithelium in biopsies from patients with renal diseases; however, their biological importance is not well understood. We reviewed ultrastructural pathology records of 140 renal biopsy patients to determine the occurrence and relevance of hyaline droplets. Of the cases, 14 (10%) showed the presence of hyaline droplets in proximal tubular epithelium. The distribution of cases were 8 of the 19 (42%) with minimal change nephritic syndrome, 2 of the 37 (5%) with IgA nephropathy, 2 of the 4 (50%) with membranous glomerulonephropathy, 1 of the 4 (25%) with tubulointerstitial nephritis, and 1 of the 1 (100%) with acute renal failure. The droplets were frequently found in male patients (86%), never in children, and were mostly associated with tubular necrosis (8 of 14 cases; 56%). Many hyaline droplets were observed in the cytoplasm of necrotic proximal tubular epithelial cells, and even when tubular necrosis was not evident, the proximal tubular epithelial cells containing hyaline droplets showed degenerated microvilli and decreased basal interdigitations. These results suggest that hyaline droplets could be one marker of renal tubular necrosis and a sign of functional disorder of protein reabsorption by degenerating proximal tubular epithelium.

Intracytoplasmic filamentous inclusions in the peripheral blood of a patient with chronic lymphocytic leukemia: A bright-field, electron microscopic, immunofluorescent, and flow cytometric study

Intracellular inclusions in lymphoproliferative disorders are not common. Multiple different types of inclusions have been reported in chronic lymphocytic leukemia (CLL), including vacuoles, crystals, and pseudocrystals. Most of the reported cases were seen in the bone marrow lymphocytes, and the majority of these on electron microscopy. We report a case of long-standing CLL with no therapy that had filamentous cytoplasmic inclusions in the peripheral blood that were readily seen by light microscopy. Electron microscopy demonstrated dilated cisternae of the rough endoplasmic reticulum filled with amorphous electron-dense material. By immunofluorescence, the material proved to be immunoglobulin G-lambda deposits. The immunophenotype had the typical CLL pattern with positive staining with CD19, CD5, and CD23, and low-density CD20 staining; however, it also had unusual staining with CD25 and intermediate-intensity staining with CD22.

The Omp85 protein of Neisseria meningitidis is required for lipid export to the outer membrane

In Gram-negative bacteria, lipopolysaccharide and phospholipid biosynthesis takes place at the inner membrane. How the completed lipid molecules are subsequently transported to the outer membrane remains unknown. Omp85 of Neisseria meningitidis is representative for a family of outer membrane proteins conserved among Gram-negative bacteria. We first demonstrated that the omp85 gene is co-transcribed with genes involved in lipid biosynthesis, suggesting an involvement in lipid assembly. A meningococcal strain was constructed in which Omp85 expression could be switched on or off through a tac promoter-controlled omp85 gene. We demonstrated that the presence of Omp85 is essential for viability. Depletion of Omp85 leads to accumulation of electron-dense amorphous material and vesicular structures in the periplasm. We demonstrated, by fractionation of inner and outer membranes, that lipopolysaccharide and phospholipids mostly disappeared from the outer membrane and instead accumulated in the inner membrane, upon depletion of Omp85. Omp85 depletion did not affect localization of integral outer membrane proteins PorA and Opa. These results provide compelling evidence for a role for Omp85 in lipid transport to the outer membrane.

Ultrastructural localization of histidine-labelled interkeratin matrix during keratinization of amphibian epidermis

Interkeratin histidine-rich proteins (filaggrins) play a functional role in aggregation of keratin filaments into dense bundles during terminal differentiation of mammalian keratinocytes when forming the dense matrix of the stratum corneum. The origin of the stratum corneum during adaptation to land in amphibious vertebrate progenitors was probably linked with the synthesis of matrix proteins. However, whether similar proteins are present in living amphibians is unknown. The possible involvement of interkeratin matrix molecules rich in basic amino acids such as histidine during keratinization of amphibian epidermis has been evaluated in the present study by ultrastructural autoradiography after administration of tritiated histidine. At 4 and 8 h post-injection, labelling was mainly localized over electron-dense amorphous material or irregular granules in between keratin filaments in cells of the upper intermedium, replacement, and immature corneous layers. Nuclear material incorporating tritiated histidine was also present in the maturing corneous layer. Small mucous-like granules did not take up tritiated histidine and X-ray microanalysis indicated that the latter granules contained sulphur. The present study suggests that small amounts of histidine-rich molecules which were not sufficient to form microscopically-visible keratohyalin granules were present in ancestral amphibian epidermis. However, this material was sufficient to promote aggregation of keratin filaments in the cytoplasm of amphibian differentiating keratinocytes, especially near the external corneous cell envelope. Electron-dense material associated with the corneous cell envelope also contained sulphur as indicated by X-ray microanalysis. It is unknown whether sulphur is derived from either sulphated mucins, or disulphide bonds in aggregated keratins, or specific sulphur-rich proteins.

Bothrops moojeni snake venom-induced renal glomeruli changes in rat.

The venom of Bothrops moojeni has potent proteolytic and phospholipase A2 activities. In previous work, we showed that intravenous injection of this venom in rats decreased creatinine clearance and caused tubular dysfunction and histopathological changes with no alterations in blood pressure. The current study used scanning and transmission electron microscopy to assess the ultrastructural changes caused by B. moojeni venom (0.4 mg/kg i.v.) in rat renal glomeruli and correlated these alterations with the severity of proteinuria 5 hours, 16 hours, and 48 hours after venom injection. The changes included mesangiolysis, glomerular microaneurysms, and glomerular basement membrane (GBM) abnormalities. In addition, there was a reduction in the number and width of podocyte pedicels, which caused a reduction in the number of filtration slits. Electron-dense amorphous material, which may be proteinaceous in origin, was found in the pedicels. The severity of the ultrastructural abnormalities correlated with the level of proteinuria. These morphophysiological changes were attributed to biochemical and physiological disturbances in the components of the GBM and mesangial matrix as well as in cytoskeleton-associated proteins of podocytic processes, and could account for the breakdown of optimal glomerular filtration barrier functioning. These results, together with the absence of appreciable glomerular fibrin deposits, support the hypothesis of a direct activity of B. moojeni venom on rat kidneys. Proteolytic activity of the venom on renal glomeruli could then contribute to the onset of acute renal failure, and would explain the clinical manifestations of renal injury after bites by this and other Bothrops species.

Ultrastructural study of the alveolar lining and the bronchial mucus layer by block staining with oolong tea extract: the role of various surfactant materials.

To investigate the roles of various surfactant materials in the lung, we examined rat lung fixed with a mixture of 0.2% oolong tea extract (which contains various polyphenols) and 2.5% glutaraldehyde by electron microscopy. We also measured the surface tension of various isolated surfactant fractions, with a Wilhelm balance. A fraction containing lamellar bodies and a fraction containing lattice-like structures were obtained by discontinuous sucrose gradient centrifugation. From the 15 000 g supernatant, a fraction containing electron-dense amorphous materials was obtained as the 105 g precipitate. The fraction containing lamellar bodies and the fraction containing electron-dense amorphous materials displayed surfactant activity, but the fraction containing lattice-like structures did not. The lamellar bodies were found to be gradually secreted from type II epithelial cells while self-decomposition occurred. The alveolar lining layer had the form of a thin film consisting of electron-dense amorphous materials. These electron-dense amorphous materials may be precursors of the phospholipid film, which exhibits surfactant activity, on the alveolar surface. Lattice-like structures and lamellar bodies were found to be located in the interalveolar pores. The interalveolar pores were filled with surfactant, and this indicated that they do not play a role in the collateral ventilation of the alveoli. It may be that the lattice-like structures serve to connect lung epithelial cells in the interalveolar pores, as well as serving as the basis for the formation of the alveolar ducts. The bronchial mucus layer, which consisted of fibrillar mucous materials, was not divided into an epiphase and a hypophase. A surfactant, in the form of an osmiophilic surface film and some trilaminar materials, was found to cover the mucus layer. Thus, it is possible that the lamellar bodies could be transformed into various surfactant materials, which then serve bronchial or alveolar mechanical and physiological functions.

Regional Distribution of Amyloid-Bri Deposition and Its Association with Neurofibrillary Degeneration in Familial British Dementia

Familial British dementia (FBD), pathologically characterized by cerebral amyloid angiopathy (CAA), amyloid plaques, and neurofibrillary degeneration, is associated with a stop codon mutation in the BRI gene resulting in the production of an amyloidogenic fragment, amyloid-Bri (ABri). The aim of this study was to assess the distribution of ABri fibrillar and nonfibrillar lesions and their relationship to neurofibrillary pathology, astroglial and microglial response using immunohistochemistry, confocal microscopy, and immunoelectron microscopy in five cases of FBD. Abnormal tau was studied with immunoblotting. We present evidence that ABri is deposited throughout the central nervous system in blood vessels and parenchyma where both amyloid (fibrillar) and pre-amyloid (nonfibrillar) lesions are formed. Ultrastructurally amyloid lesions appear as bundles of fibrils recognized by an antibody raised against ABri, whereas Thioflavin S-negative diffuse deposits consist of amorphous electron-dense material with sparse, dispersed fibrils. In contrast to nonfibrillar lesions, fibrillar ABri is associated with a marked astrocytic and microglial response. Neurofibrillary tangles and neuropil threads occurring mainly in limbic structures, are found in areas affected by all types of ABri lesions whereas abnormal neurites are present around amyloid lesions. Immunoblotting for tau revealed a triplet electrophoretic migration pattern. Our observations confirm a close link between ABri deposition and neurodegeneration in FBD.