Lysosomal “mottled appearance”, or uneven electron-dense content related to monoclonal gammopathy (MG), has been mainly described in light chain proximal tubulopathy (LCPT). We aimed to determine the ultrastructural characteristics of lysosomal mottled appearance in kidney biopsies and its association with LCPT and MG. Seventy-seven biopsies were grouped into LCPT (n = 5), MG conditions other than LCPT (n = 43), and non-MG conditions (n = 29). The mottled lysosomes in the renal tubules were evaluated using transmission electron microscopy and morphometric analysis. Mottled lysosomes were more prevalent (% of present cases) and frequent (no. of mottled lysosomes/20,000× ultramicroscopic field) in the LCPT group (100% and 8.20 ± 4.15/field) than in the MG (41.9% and 1.13 ± 2.05/field) and non-MG (37.9% and 0.80 ± 1.44/field) groups. In morphometric analysis of all mottled lysosomes (n = 520) detected from the 34 biopsies (5 LCPT, 18 MG, and 11 non-MG), we found that mottled lysosomes were larger, more irregular, and more electron-dense for the LCPT group than for the MG and non-MG groups. Therefore, mottled lysosomes can be present in disorders other than LCPT or even without MG. The morphological characteristics of mottled lysosomes could provide objective guidance for the diagnosis of LCPT.

The size of gold nanoparticles (AuNPs) can influence various aspects of their cellular uptake. Light microscopy is not capable of resolving most AuNPs, while electron microscopy (EM) is not practically capable of acquiring the necessary statistical data from many cells and the results may suffer from various artifacts. Here, we demonstrate the use of a fast EM method for obtaining high-resolution data from a much larger population of cells than is usually feasible with conventional EM. A549 (human lung carcinoma) cells were subjected to uptake protocols with 10, 15, or 30 nm diameter AuNPs with adsorbed serum proteins. After 20 min, 24 h, or 45 h, the cells were fixed and imaged in whole in a thin layer of liquid water with environmental scanning electron microscopy equipped with a scanning transmission electron microscopy detector. The fast preparation and imaging of 145 whole cells in liquid allowed collection of nanoscale data within an exceptionally small amount of time of ~80 h. Analysis of 1,041 AuNP-filled vesicles showed that the long-term AuNP storing lysosomes increased their average size by 80 nm when AuNPs with 30 nm diameter were uptaken, compared to lysosomes of cells incubated with AuNPs of 10 and 15 nm diameter.

Previous studies have described promising antitumor activity of an organometallic Ru(II) complex, η5-Cyclopentadienyl(2,2′-bipyridyl)(triphenylphosphane) Ruthenium(II) triflate ([(η5-C5H5)Ru(2,2′-bipyridyl)(PPh3)][CF3SO3]) herein designated as TM34. Its broad spectrum of activity against a panel of human tumor cell lines and high antiproliferative efficiency prompted us to focus on its mode of action. We present herein results obtained with two human tumor cell lines A2780 and MDAMB231 on the compound distribution within the cell, the mechanism of its activity, and its cellular targets. The prospective metallodrug TM34 revealed: (a) fast antiproliferative effects even at short incubation times for both cell lines; (b) preferential localization at the cell membrane and cytosol; (c) cellular activity by a temperature-dependent process, probably macropinocytosis; (d) inhibition of a lysosomal enzyme, acid phosphatase, in a dose-dependent mode; and (e) disruption and vesiculation of the Golgi apparatus, which suggest the involvement of the endosomal/lysosomal system in its mode of action. These results are essential to elucidate the basis for the cytotoxic activity and mechanism of action of this RuII(η5-cyclopentadienyl) complex.

A one-month-old boy, with type-II mucolipidosis, presented with congestive heart failure and elevated cardiac enzymes. The atretic nature of the orifice of the left coronary artery was revealed by retrograde flow on color Doppler and selective coronary angiography. Type-II mucolipidosis and atresia of the left coronary artery are rare. To the best of our knowledge, this is the first report of their combined occurence, suggesting a possible causal relationship.

Bacillus sphaericus (Bs) is a potential mosquito larvicide especially against Culex quinquefasciatus (Say), the vector of bancroftian filariasis. It is a gram-positive, aerobic and endospore-forming bacterium. During sporulation, it synthesizes binary endotoxins (molecular weight 42 and 51 kDa proteins) that are highly toxic to mosquito species. The mode of action of the binary toxin of this biolarvicide in the alimentary canal and the ultrastructural events in the tissues of the affected larvae have been demonstrated. Lysosomal components are the most important organelles involved in the metabolism of the foreign molecules encountered by the cells. In this paper, we report the ultrastructural changes in the midgut epithelial cells, with special emphasis on lysosomes (L), in untreated Cx. quinquefasciatus larvae and those treated with the Bs-IAB59 bacterial strain. In the Bs-treated larvae, the size of the L gradually increased, and within 16 h, fine filaments appeared and compartmentalized into small lamellar bodies, within the L. After 36 h, these lamellar bodies appeared to be collapsed, and later disintegrated in the 48th hour. In the untreated larvae, such ultrastructural changes in the L were not seen. These observations suggested that, though the target site of action of the Bs toxin is the midgut epithelial cells, ultrastructural changes in the L compartments play a vital role in the mortality of the mosquito larvae.

The cercariae of Schistosoma mansoni become transformed into schistosomula during host skin penetration. We have found that large acidophilic compartments are detected in schistosomula but not in cercariae or in any other stages of the parasite by use of the fluorescent dye LysoTracker, a dye specific for mammalian lysosomes. Some of these large acidic compartments incorporated monodansylcadaverine, a specific dye for autophagosomes. We have used potent inhibitors (wortmannin and 3-methyladenine) and a potent inducer (starvation) of autophagy to show that the pathway to the formation of the acidic compartments requires specific molecular signals from the environment and from the genome. Certain doses of ultraviolet light inhibited significantly the formation of the acidic compartments, which may indicate disruption of the lysosome/autophagosome pathway. We have also defined two proteins that are commonly associated with lysosomes and autophagosomes in mammalian cells, the microtubule-associated membrane protein (MAP-LC3) and lysosome-associated membrane protein (LAMP-1), in extracts of schistosomula. We suggest that the autophagy pathway could be developed in transformed schistosomula.

Sixteen biopsies of rhinosporidiosis (15 nasal and one conjunctival) from 16 Southern Indian male immigrant workers showed mucosal lymphoplasmacellular infiltrates together with transepithelial elimination of nodular bodies and destruction of some late stage nodular bodies in histiocytic granulomata with central neutrophilic microabscesses. Early nodular bodies were immunohistochemically positive for alpha1-AT, alpha1-ACT, CEA, S100, fibronectin, amyloid-p-component, IgG, IgA, CIq and C3. Electron microscopy showed organized

concentric lamellated bodies in early nodular bodies and not in end-stage nodular bodies which contained mostly amorphous electron dense materials. Structures formerly regarded as ‘sporangia’ and ‘spores’ are believed to be lysosomal bodies loaded with indigestible residues to be cleared via transepithelial elimination or segregated/destroyed by secondary immune/granulomatous responses.