[Classification and therapeutic management of monoclonal gammopathies of renal significance]. / Classification et prise en charge thérapeutique des gammapathies monoclonales de signification rénale.

Two categories of renal disorders associated with monoclonal gammopathies are to be distinguished, according to the characteristics of the underlying B-cell clone. The first group of renal diseases always occurs in the setting of high tumor mass with production of large amounts of monoclonal immunoglobulins. The main complication is the so-called myeloma cast nephropathy, which almost invariably complicates high tumor mass myeloma. The second group includes all renal disorders caused by a monoclonal immunoglobulin secreted by a nonmalignant B-cell clone, and currently referred as a "monoclonal gammopathy of renal significance (MGRS)". This term was introduced to distinguish monoclonal gammopathies that are responsible for the development of kidney damage from those that are truly benign. The spectrum of renal diseases in MGRS is wide and its classification relies on the localization of renal lesions, either glomerular or tubular, and on the pattern of ultrastructural organization of immunoglobulin deposits. Physicochemical characteristics of the pathogenic monoclonal immunoglobulin are probably involved in their propensity to deposit or precipitate in the kidney, as illustrated by the high rate of recurrence of each specific type after kidney transplantation. Early diagnosis and efficient chemotherapy targeting the causal B-cell clone are mandatory to improve renal prognosis and patient survival.

The Na, K-ATPase alpha3-isoform specifically localizes in the Schmidt-Lanterman incisures of human nerve.

INTRODUCTION: To our knowledge, there is little reference in literature with regards to alpha3-isoform of Na+,K+-ATPase in human peripheral nerves. The aim of this study was to determine the expression of the neuronal alpha3-isoform of Na+,K+-ATPase in human sural nerves from patients with a permanent medullary central nervous system injury. MATERIALS AND METHODS: We studied the immunolocalization of alpha3-isoform of Na+,K+-ATPase using a polyclonal antibody against the amino sequence near the phosphorylation site of the alpha3-isoforms of Na+,K+-ATPase using immunohistochemistry and confocal laser scanning microscopy. An antibody specific for alpha2-isoform of Na+,K+-ATPase was used to label the Schwann cells. RESULTS: Morphometric analysis of longitudinal section of human sural nerves showed that the alpha3-isoform of Na+,K+-ATPase was distributed along the length of axolemma. The myelin sheath of the Schwann cells showed clearly a distribution of alpha3- but not alpha2-isoforms of Na+,K+-ATPase at the level of Schmidt-Lanterman incisures. CONCLUSION: The human sural nerve shows a specific localization of the Na+,K+-ATPase alpha3-isoform in the Schmidt-Lanterman incisures of Schwann cells in addition to its localization in axonal membranes.

[Ultrastructural study of epiretinal membrane stained by trypan blue: 15 case reports]. / Etude ultrastructurale des membranes épirétiniennes idiopathiques colorées au bleu trypan.

INTRODUCTION: Idiopathic epiretinal membrane results from detachment of the posterior hyaloid and is believed to be related to naturally occurring defects in the internal limiting membrane (ILM) of the retina. Vitrectomy and peeling are the treatment of choice. Trypan blue 0.15% (TB) stains epiretinal membrane and internal limiting membrane. It allows selective and complete removal, facilitating surgery, with less retinal damage. An ultrastructural study was conducted showing ultrastructural features of idiopathic epiretinal membranes (ERM) and those of the internal limiting membrane and its connections with the retinal side. MATERIAL AND METHODS: After pars plana vitrectomy and induction of posterior vitreous detachment, 0.2 ml TB 0.15% was injected over the ERM in an air-filled eye. The stained tissue was peeled with intraocular forceps. Specimens were at once collected in 4% glutaraldehyde for a transmission electron microscopy study. RESULTS: TB may allow complete and easier ERM and ILM peeling. The staining does not present toxic effects. The major cellular contingent is represented by glial cells, participating actively in neocollagen synthesis. Their presence supports the hypothesis of a migratory movement of retinal cells toward the vitreoretinal side. CONCLUSION: The presence of an intact internal limiting membrane, the absence of optical fibers belonging to the under retina, and the absence of any sign of apoptosis make TB a useful staining agent for ERM and ILM peeling.

Cadmium-containing granules in kidney tissue of the Atlantic white-sided dolphin (Lagenorhyncus acutus) off the Faroe Islands.

Top predators from the northern sub-polar and polar areas exhibit high cadmium concentrations in their tissues. In the aim to reveal possible adverse effects, samples of five Atlantic white-sided dolphins Lagenorhyncus acutus have been collected on the occasion of the drive fishery in the Faroe Islands, for ultrastructural investigations and energy dispersive X-ray microanalyses. Cadmium concentrations were less than the limit of detection in both immature individuals and ranged from 22.7 to 31.1 microg x g(-1) wet weight in the mature individuals. Two individuals with the highest cadmium concentrations exhibited electron dense mineral concretions in the basal membranes of the proximal tubules. They are spherocrystals made up of numerous strata mineral deposit of calcium and phosphorus together with cadmium. Cadmium has been detected with a molar ratio of Ca:Cd of 10:1 in the middle of these concretions. To our knowledge, this is the first report of such granules in a wild vertebrate. The role of these granules in the detoxification of the metal and the possible pathological effects are considered.

Ultrastructural study of rat hippocampus after chronic administration of aluminum L-glutamate: an acceleration of the aging process.

An ultrastructural study of rat hippocampus was performed on young (group 1) and old (group 4) rats receiving daily subcutaneous injections of aluminum L-glutamate and on old untreated rats (group 5). Young controls were treated with sodium L-glutamate (group 2) and physiological saline (group 3). Group 1 showed vacuolated astrocytes with numerous lipofuscin deposits, mitochondrial swelling, a thinning of the myelin sheath, and many multivesicular bodies invading the cytoplasm. Cellular structure did not appear to be affected in groups 2 and 3. Group 4 showed swollen mitochondria, a demyelination process in axonal regions, sizable perivascular oedema with vessel retraction and gliofilament bundles. In this group, lipofuscin deposits in astrocytes were associated with multivesicular bodies that thinned the myelin sheath to the breaking point; however, no excitotoxic glutamate-induced effects were observed. In group 5, extreme cytoplasmic vacuolation was observed, with massive mitochondrial swelling, considerable thinning of the myelin sheath (at times to the breaking point), sizable vacuolar degeneration and gliofilament bundles. These results indicate that ultrastructural alterations in the hippocampus, such as cell vacuolization, massive mitochondrial swelling and the demyelination process, occur with aging and independently of aluminum intoxication. Similar alterations were observed in aluminum L-glutamate-intoxicated young rats, but not in controls. These results are consistent with aluminum-induced acceleration of the aging process.

Chronic administration of aluminium L-glutamate in young mature rats: effects on iron levels and lipid peroxidation in selected brain areas.

Clinical and experimental studies have demonstrated the neurotoxicity of aluminium (Al), notably as a result of lipid peroxidation in vitro. We previously showed that Al is able to cross the blood-brain barrier as an L-glutamate complex and be deposited in rat brain. The present work in young mature rats investigated the in vivo effects of chronic Al-L-glutamate treatment on Al and iron movement in plasma and selected brain regions. Brain lipid peroxidation was determined by evaluating the production of thiobarbituric acid reactive substances (TBARS) and analysing polyunsaturated fatty acids (PUFAs) such as C20:4n-6 and C22:6n-3. Our results indicate that iron concentration was decreased in plasma and that Al accumulated especially in striatum where iron levels were decreased and in the hippocampus where TBARS were increased without PUFA modifications. These data show that Al administered chronically as an L-glutamate complex is neurotoxic in vivo and thus provides a good model for studying Al toxic mechanisms.

Expression, localization, and thyrotropin regulation of cathepsin D in human thyroid tissues.

Enzymatic activity and isoform expression of cathepsin D (cath D) were studied in 107 cytosols from various human thyroid tissues including 21 normal tissues, 12 cold benign nodules, 17 toxic adenomas, 22 samples from Graves' disease patients, and 35 thyroid carcinomas. Cath D assay was optimized for human thyroid tissues. We found that mean cath D specific activities, expressed as units per milligrams protein minus thyroglobulin, were higher in carcinomas (P = 0.0001), toxic adenomas (P = 0.0001), and specimens from Graves' disease patients (P = 0.0001) than in normal thyroid tissues. Mean cath D activity in carcinomas was also significantly different from that in cold benign nodules (P < 0.001) and Graves' disease tissues (P < 0.05) but not from that of toxic adenomas. To determine possible mechanisms by which the observed increase in cath D activity might be regulated, we used Western blotting to measure relative amounts of cath D isoforms in the various thyroid tissues. We found that the 31-kDa major processing form of cath D was significantly increased in carcinomas and toxic adenomas compared with normal tissues (P < 0.01), cold benign nodules (P < 0.05), and Graves' disease tissues (P < 0.05). A positive correlation of cath D activity with relative expression of the 31-kDa form (r = 0.67, P = 0.0001) was observed in 104 thyroid cytosols. These data demonstrate a deregulation at the protein level, with resulting increases in cath D activity. Immunogold labeling of cath D showed particle concentration in lysosomes or phagosomes in both normal follicles and papillary carcinoma cells, indicating that cath D localization was not altered by malignant transformation in human thyroid cells. TSH induced cath D synthesis and secretion in extracellular fluid of normal human thyroid cells in primary culture; TSH had little effect on intracellular cath D level. In conclusion, TSH-induced cath D synthesis may explain high cath D levels in Graves' disease tissues and toxic adenomas, because these tissues possess a permanently stimulated cAMP transduction pathway. Furthermore, the overexpression of cath D in thyroid carcinomas in comparison with normal controls adds further arguments for the potential role of cath D in tumor growth and metastasis.

Changes in Helicobacter pylori ultrastructure and antigens during conversion from the bacillary to the coccoid form.

In vitro, Helicobacter pylori converts from a bacillary to a full coccoid form via an intermediate U-shaped form. Organisms with a full coccoid form keep a double membrane system, a polar membrane, and invagination structures. Western blots (immunoblots) of sera from colonized patients show that some high-molecular-mass antigenic fractions are expressed only in coccoids. Conversely, fractions of 30 and 94 kDa were more intensively detected in the bacillary forms. These results suggest that (i) coccoid conversion is not a degenerative transformation and (ii) antigens specific to the coccoid forms are expressed in vivo.

Detection of myosin immunoanalogue in the yeast Candida albicans.

Detection and localization of myosin immunoanalogue protein in the yeast Candida albicans were achieved by immunoblotting, indirect immunofluorescence assay, and immunoelectron microscopy. A polypeptide with an M(r) about 110,000, from cytosolic extract and insoluble fraction in the corresponding membrane pellet, was reacted with polyclonal and monoclonal antibodies raised against vertebrate muscle myosin. This protein was located by immunofluorescence and immunoelectron microscopy in the cell cortex along the plasmalemma, in the cytoplasm, and in the septum corresponding to bud scar region situated between the yeast-mother cell and the bud.