Biomedical subjects

S Lhoták

Publications and source records attributed to S Lhoták.

8 recordsLinked to original sources

PubMed2002

Morphological, histomorphometric, and microstructural alterations in human bone metastasis from breast carcinoma.

Bone is one of the most common sites of breast cancer metastasis. Metastases are often associated with bone destruction and are a major cause of morbidity. We examined structural bone changes induced by metastatic tumor in bone biopsies from 33 patients with metastatic breast carcinoma (20 from patients with pathological femoral fracture and 13 with no fracture) and 20 normal controls. In all metastatic biopsies bone remodeling was shown to be tumor volume-dependent. Bone resorption and bone formation were biphasic with both increasing at earlier stages of metastatic bone disease and decreasing later on. A comparison of patients with fracture and no fracture did not reveal statistically significant differences in the extent of bone destruction or trabecular thinning. Bone histomorphometry showed limited ability to explain the higher bone volume loss in fracture patients (decreases of 42% and 25%, respectively, in fracture and nonfracture patients compared with controls). However, changes in bone quality, including increased disconnectivity and decreased connectivity, as evaluated by node-strut analysis, suggested that there were more structural changes in the fracture compared with the nonfracture group. The nonfracture group included six patients with no radiological evidence of bone metastasis (occult metastasis). They showed a higher tumor volume and a twofold lower eroded surface compared with the rest of the group. The decrease in bone volume (14% lower than controls) was below the limit of X-ray detection. Because we observed no increase in osteoclast-related parameters and no correlation between osteoclast surface and eroded surface, we believe that, in occult metastasis, osteoclastic bone resorption is not an important factor in overall bone resorption. Quantitatively, the eroded surface in direct contact with tumor cells was threefold higher than the osteoclast surface in occult metastasis, whereas the rest of the metastatic group (27 of 33) showed predominantly osteoclast-mediated eroded surface. Node-strut analysis on occult metastasis revealed a significant increase in disconnectivity without a concomitant significant decrease in bone volume and trabecular thinning. We conclude that, in occult metastasis, bone resorption may be more osteoclast-independent and other mechanisms involving the tumor cells may be more prevalent.

Adult↗

PubMed2000

Evidence that colitis is initiated by environmental stress and sustained by fecal factors in the cotton-top tamarin (Saguinus oedipus).

Parallel changes in spontaneously occurring inflammation in colonic Thiry-Vella loops and the in-line colon of cotton-top tamarins were studied in a colitis-inducing environment at 8 and 15 months following surgical preparation of the loops. Gross disease severity and numbers of inflammatory/immune cells per unit area of lamina propria in histological sections from endoscopic biopsies were analyzed. Cell counts and severity of colitis declined over time in the Thiry-Villa loops while the disease followed its characteristic course in the remaining large bowel and in the colons of controls. Perfusion of the loops with the animals' feces increased the density of the cellular infiltrate in the lamina propria in parallel with increased severity of inflammation. Electron micrographs of the colonic mucosa showed invasion by microorganisms. The predominant microorganism had characteristics of Helicobacter sp. The results implicate the fecal stream as a factor in the persistence of colitis in the tamarin model. Nevertheless, fecal factors appear not to be the primary trigger, as evidenced by findings that the disease is not expressed in wild-living tamarins and that it enters remission when affected animals are transferred to natural conditions from a colitis-inducing environment. Both an adverse environment and the fecal contents appear to be required for expression of the disease.

Animals↗

PubMed2000

Immunolocalization of matrix metalloproteinases and their inhibitors in clinical specimens of bone metastasis from breast carcinoma.

Matrix metalloproteinases (MMPs) are essential in several stages of the metastatic process, and in normal bone development and remodeling. We explored whether the interaction between tumor cells and bone leads to changes in MMP and tissue inhibitor of MMP (TIMP) expression thus affecting osteolysis in metastatic bone disease. Using immunohistochemistry we have investigated the MMP/TIMP expression in tumor cells, fibroblasts, osteoblasts and osteoclasts. Thirty one specimens of bone metastasis from breast carcinoma were stained for MMP-1, -2, -9, MT1-MMP and TIMP-1, and -2 and compared with staining in normal breast tissue, primary breast carcinoma and normal bone. Specimens came from patients in three clinical scenarios: from open biopsies without or with pathological fracture, or bone marrow biopsies containing tumor from patients with pancytopenia but without clinical evidence of osteolysis. By bone histomorphometry the latter group showed a heavy tumor load not different from the open biopsy groups but displayed little active bone resorption and low numbers of osteoclasts. Cell type-specific MMP/TIMP expression was observed and the staining patterns were comparable between the three groups of patients. Though no major differences in the MMP/TIMP staining of tumor cells and fibroblasts were observed between bone metastasis and primary tumor, we showed that tumor cells do express MMPs capable of degrading bone matrix collagen. The number and activity of osteoclasts and osteoblasts was increased dramatically in bone metastases, their MMP/TIMP profiles, however, were not different from normal bone, suggesting that the mechanism of bone degradation by osteoclasts is not different from normal bone remodelling.

Bone Neoplasms↗

PubMed1998

Taxol involution of collagen-induced arthritis: ultrastructural correlation with the inhibition of synovitis and neovascularization.

Collagen-induced arthritis (CIA) is an animal model of rheumatoid arthritis (RA) that can be regressed with Taxol (paclitaxel), a chemotherapeutic agent. To identify structural changes that occur with involution, the synovium from naive, untreated CIA, and Taxol-treated CIA rats were evaluated by light microscopy plus transmission and scanning electron microscopy. Analysis included detailed images of vascular networks using polymeric corrosion casts. The CIA synovium was morphologically similar to human RA synovium. In CIA, the integrity of the intimal lining is lost by Type-B synoviocytes becoming highly elongated and polarized toward the joint space, resulting in non-overlapping cellular processes and the elimination of the basal lamina. In addition, the lining expanded from a width of 6-10 microns in naives to 200-250 microns in CIA due primarily to increased numbers of both Type-A and -B synoviocytes and more interstitial matrix. Vascular corrosion casts of CIA synovium illustrated a marked increase in blood vessel volume and an extensive interconnecting vascular architecture; neovascular arrays were observed to project toward the synovial surface. In Taxol-treated CIA, the synoviocyte and neovascular components reverted to the naive synovium morphology, suggesting that this agent might be useful in the therapy of RA.

Animals↗

PubMed1997

Effect of truncal vagotomy and capsaicin on mast cells and IgA-positive plasma cells in rat jejunal mucosa.

Immunocompetent cells, including mast cells and plasma cells (PC), in the intestinal mucosa are closely apposed to nerve fibres. Recent work has shown that vagal afferent nerves penetrate the jejunal mucosa and contact intestinal mucosal mast cells (IMMC); and that electrical stimulation of the vagus results in increased IMMC histamine content. To determine if the vagus nerve exerts a trophic effect on immunocompetent cells in the gut mucosa, the effects of truncal vagotomy and neonatal capsaicin treatment on IMMC and IgA containing PC in the lamina propria of rat jejunum were investigated. Three weeks after vagotomy, microdensitometric assessment of Alcian blue stained sections revealed 25% fewer IMMC in vagotomized animals than in controls (P < 0.05). Three months after neonatal capsaicin administration 28% fewer IMMC were found in treated rat jejunum, compared with littermate controls (P < 0.05). Three weeks post-surgery, IgA-PC densities were increased in both vagotomized animals (that also underwent pyloroplasty) and pyloroplasty controls, compared to animals subjected to laparotomy only. The proportion of lamina propria areas remained stable, indicating that the observations reflected real reductions in the numbers of IMMC. We also determined the densities of B-50 (a nerve growth-associated protein, also called GAP-43) immunoreactive nerve fibres in the lamina propria, as well as nerve profile areas, three weeks after vagotomy, and these parameters were unchanged. Taken together, these findings support the hypothesis that the vagus exerts a trophic effect on IMMC; and that capsaicin-sensitive nerves also affect the IMMC population. These data add to the growing body of evidence for a functional connection between IMMC and the nervous system.

Animals↗

PubMed1995

Electrical stimulation of the vagus nerve modulates the histamine content of mast cells in the rat jejunal mucosa.

Mast cells are best known for their participation in allergic reactions. However, a number of recent studies suggest that mast cells are subject to nervous control. In the gut mucosa, mast cells are intimately associated with nerves, and the psychologically conditioned release of RMCP II (a mucosal mast cell-derived mediator) has been reported. These data suggest the potential for CNS regulation of intestinal mucosal mast cells. In this study, we stimulated the cervical vagi and found an increased histamine content in mucosal mast cells, without apparent degranulation. Furthermore, these changes could be prevented by subdiaphragmatic vagotomy. These data support the potential for intestinal mucosal mast cell regulation by the central nervous system and suggest modulation of mast cells without degranulation.

Analysis of Variance↗

PubMed1995

Ultrastructural examination of B-50(GAP-43) immunoreactivity in rat jejunal villi.

The lamina propria of rat jejunum is densely innervated with nerve fibres extending to the tips of the villi. A large number of these nerve fibres were previously shown to be B-50-immunoreactive at the light microscope level, whereas neurofilament immunoreactivity was found to be sparse in the mucosa. In this study we used immunoelectron microscopy to determine what proportion of nerve fibres in the lamina propria express B-50. Jejuna from male Lewis rats were immunolabelled for B-50 and neurofilament proteins. For electron microscopy, postembedding immunogold-silver techniques and LR White embedded tissues were used. Light microscopical immunostaining was performed by the streptavidin-biotin-peroxidase technique on deparaffinized tissue sections. We found that all ultrastructurally identifiable nerve profiles in jejunum were B-50 immunoreactive. Immunoelectron microscopy for neurofilament proteins failed to label fibres in the villi, whereas myelinated nerves in tongue sections processed in parallel (positive controls) were strongly neurofilament-protein-immunoreactive. The dominant B-50-positive and neurofilament-protein-negative phenotype supports the hypothesis of ongoing modelling or plasticity of intestinal mucosal nerves.

Animals↗

PubMed1989

Immunoelectron microscopic diagnosis in nephropathology.

An immunogold postembedding method for the ultrastructural localization of immunoglobulin G (IgG), IgA, IgM, C3, fibrinogen, and kappa and lambda immunoglobulin light chains was established. The method was performed on surplus tissue from renal biopsies fixed in 2% glutaraldehyde and embedded in acrylic LR White resin. Fifteen cases were studied and the localization of antigen in the dense deposits in glomeruli compared with the immunofluorescence (IF) findings on the same cases. The results obtained by IF and immunoelectron microscopy (IEM) were comparable for IgG and IgA. In most instances, IgM and C3 were more intensely labeled by IF than IEM. Some discrepancies were noted for fibrinogen. It is postulated that these differences are related to a partial loss of antigenicity due to fixation or chemical reaction with the embedding medium. The advantage of IEM resides in localizing antigens in very small deposits seen in early stages of glomerulonephritis. The method can supplement IF in diagnostically difficult cases or be substituted for it when material for IF is not available.

Complement C3↗