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Biomedical subjects

L Sosula

Publications and source records attributed to L Sosula.

12 recordsLinked to original sources

Heterotransplantation of human lymphoid neoplasms using a nude mouse intraocular xenograft model.

There are few effective models for the study of human lymphoid neoplasms, including in vivo xenografts in immunocompromised animals. Exploiting the additional immune privilege of the anterior chamber of the nude mouse eye, a novel method of direct heterotransplantation of cells from childhood leukemias and lymphomas has been developed. The establishment and characterization of 18 lymphoid xenograft cell lines maintained in the nude mouse intraocular model are reported. Cell sources for heterotransplantation were specimens of bone marrow, peripheral blood, or lymphomatous masses obtained at either diagnosis or recurrence of disease in the patients. The 18 patients and resultant cell lines were grouped into four immunophenotypic categories: Category 1, B-lineage (pre-B and early pre-B), "common" acute lymphatic leukemias; Category 2, cell lines of similar immunophenotype derived from patients with unusual features; Category 3, B-cell neoplasms and cell lines; and Category 4, neoplasms and cell lines in part or totally of T-cell origin. With reference to these groupings, rates of ingraftment from clinical specimens varied according to immunophenotype and disease status: Category 1, 1 of 15 at diagnosis, 5 of 7 at relapse; Category 2, 1 of 1 at diagnosis, 2 of 2 at relapse; Category 3, 6 of 6 at diagnosis; and Category 4, 2 of 9 at diagnosis, 1 of 1 with persistent disease. Rearrangements of the genes for immunoglobulin heavy chain or kappa light chain and for beta subunit of the T-cell receptor gene were demonstrated according to immunophenotype, with the exception of one cell line which showed no rearrangements. Evidence of Epstein-Barr virus DNA was shown in only one cell line, of B-cell immunophenotype. Cytology, histopathology, and electron microscopy in representative patient and xenograft samples demonstrated correlations between the specimens of origin and cells or sections from ingrafted tumors in mice. It is concluded that the direct heterotransplantation of cells from childhood leukemias and lymphomas to the anterior chamber of the nude mouse eye provides a relevant and reproducible model for the maintenance and study of human lymphoid neoplasms.

Animals

Therapy-induced drug resistance in a human leukemia line (LALW-2). A clinically relevant model.

A human leukemic T-cell line, LALW-2, established by xenografting in nude mice, has been maintained through 14 serial passages. The cells display consistent morphologic features, immunophenotype, and karyotypic aberrations (including an 11;14 translocation) and exhibit rearrangement of the T-cell receptor beta-chain gene. The growth rate of LALW-2 xenografts was differentially affected by drugs administered to host mice, the cells being resistant to cytotoxic agents (particularly methotrexate and doxorubicin) used in treatment of the donor patient. In short-term in vitro culture, LALW-2 cells exhibited extreme resistance to methotrexate and were also resistant to vincristine, vinblastine, dactinomycin, and doxorubicin. The findings differ from those obtained with laboratory-derived methotrexate or multidrug-resistant cell lines. The response of LALW-2 cells, in both the nude mouse model and in vitro, is consistent with acquisition of drug-resistance as a result of clinical treatment.

Animals

Ultrastructure of Campylobacter jejuni in gamma-irradiated mouse jejunum.

This paper describes the ultrastructure of intracellular elongated, transitional and coccoid forms of Campylobacter jejuni, in irradiated mouse jejunum infected both in vitro and in vivo and in cultured human skin fibroblasts. Jejunum of irradiated mouse incubated for 1 hour under conditions favorable to the organisms showed minimal tissue degeneration. The intracellular organisms in this material were free cytoplasmic forms showing inner membrane degeneration, loss of cytoplasmic granules, and absence of flagella. The diameter of the coccoids was up to four times that of the elongated forms, as in plate cultures. Intracellular organisms were not found in challenged unirradiated controls, indicating that irradiation of mouse cells may be required for intracellular infection with human strains of C jejuni. In contrast, challenged human fibroblasts contained typical elongated organisms in cytoplasmic vacuoles. These findings are discussed with reference to Campylobacter strain, host resistance, and "natural" animal and human Campylobacter infections.

Animals

Sialuria: a second case.

A case of sialuria is described in a girl who presented in the neonatal period with hepatosplenomegaly, and who has moderate developmental delay at the age of 2 years. There was massive urinary excretion of free sialic acid (N-acetylneuraminic acid). The clinical, biochemical and ultramicroscopical features were distinct from those described in Salla disease and in infantile sialic acid storage disorder.

Child, Preschool

Transmission of rotavirus gastroenteritis from children to a monkey.

A pooled suspension of rotavirus was prepared from the stools of eight children with acute non-bacterial gastroenteritis. The suspension was infused into the duodenum and stomach of an infant monkey (Nemestrina macaque). Biopsy samples of duodenal mucosa were taken at several intervals after inoculation, examined by light and electron microscopy, and assayed for lysosomal activity. Virus-like particles were seen within and around microvilli and intracellularly within vesicles as early as 20 minutes after the infusion. On the fourth and fifth days, large lysosomal bodies containing numerous virus-like particles were found within epithelial cells of the duodenal villi. No such particles were seen in the pre-inoculation sample or at days 16 or 25 after infection. The present study would appear to be the first demonstration of the transmission of this human virus to another species.

Animals

Retinal capillary junctions: ultrastructural tight junction artefacts induced by sodium ions and membrane reduction in streptozotocin diabetes.

Retinal capillary junctions were analysed in normal and diabetic rats and in a human retina with the electron microscope. Diabetes mellitus was induced with streptozotocin. The retinae were fixed in Palade's osmium tetroxide containing sodium or calcium ions and block-stained in uranyl acetate. With Ca-fixation, no significant difference in interendothelial cleft width was detected between retinal layers or between normal and diabetic retinae. Diabetes caused a narrowing of the clefts in the Na-fixed tissue X +/- SE, n=375; Normal: 78.6 +/- 300 A; Diabetic: 57.7 +/- 2.42 A; p less than 0.001). A significant correlation was found between cleft width and the length of the tight junctions or zonulae occludentes (p less than 0.001). In the nerve fibre layer of the Na-diabetic retina, where cleft narrowing was greatest, there was an increase in length of the zonulae occludentes from 22.8 +/- 2.2% to 41.6 +/- 3.7% (p less than 0.001). Ca-fixation prevented these changes, indicating that at least some zonulae occludentes were interendothelial extraction artefacts. In the normal retina, endothelial cell membrane thickness was greater with Ca- than Na-fixation (p less than 0.001). Diabetes caused a decrease in membrane thickness of Ca-fixed tissue (p less than 0.001). The diabetic decrease in membrane thickness may explain the increased fragility and increased permeability of diabetic capillaries. Calcium binding by endothelial cell membranes is of primary importance in anticoagulation which is defective in diabetes.

Animals