Biomedical subjects

S O Southern

Publications and source records attributed to S O Southern.

10 recordsLinked to original sources

PubMed2000

A nonpeptide integrin antagonist can inhibit epithelial cell ingestion of Streptococcus pyogenes by blocking formation of integrin alpha 5beta 1-fibronectin-M1 protein complexes.

Streptococcus pyogenes can be efficiently internalized by a variety of human epithelial cells. beta-lactam antibiotics, commonly used to treat S. pyogenes infections, do not readily permeate mammalian cells. There is growing evidence that the ability of streptococci to enter host cells contributes to the frequent failure of antibiotics to eradicate the organism from infected individuals. Recent studies have suggested that host cell entry requires the formation of a complex of a bacterial fibronectin (Fn) binding protein (e.g., M1 protein or protein F1/SfbI), human Fn, and the epithelial cell Fn receptor, integrin alpha5beta1. We report here that a low molecular weight, nonpeptide antagonist of integrin alpha5beta1, SJ755, can inhibit internalization of streptococci by primary human tonsillar epithelial cells and immortalized human epithelial (A549) cells, thus increasing the extent of bacterial killing by antibiotics. SJ755 blocked Fn binding by human tonsillar epithelial and A549 cells, suggesting that integrin alpha5beta1 is the major Fn receptor expressed by both cell types. SJ755 did not affect Fn binding by purified M1 protein or M1(+) bacteria. Purified M1 protein failed to associate with integrin alpha5beta1 unless the integrin had been prebound by Fn. Also, SJ755 blocked formation of alpha5beta1-Fn-M1 complexes in vitro. These results support the previous proposal that Fn functions as a molecular bridge between M1 protein and integrin alpha5beta1. Furthermore, these results suggest that integrin antagonists may enhance the efficacy of antibiotics in treatment of S. pyogenes infections.

Adhesins, Bacterial↗

PubMed2000

Clinicopathological studies of a patient with adult T-cell leukemia and pseudogynecomasty.

We present a rare case of adult T cell leukemia/lymphoma (ATL) in which leukemic T cells expressed CD4 and CD25 surface antigens and infiltrated mammary glands during clinical course of the disease. A 40-year-old male was admitted with long-standing skin lesions and leukocytosis. Peripheral blood lymphocytes were highly pleomorphic and presented CD2, CD4, CD25, CD38 membrane surface antigens. The patient proved to be seropositive for human T-cell lymphotropic virus type I (HTLV-I) antibodies. Monoclonal expansion of lymphoid cells integrated with HTLV-I genome was observed, and the diagnosis of ATL chronic type was made. He underwent a chemotherapy regimen, and skin lesions and leukocytosis improved markedly. He progressed with an indolent clinical course of ATL, when he was admitted with bilateral hyperplasia of breast, recurrent skin lesions, and leukocytosis. Breast biopsy revealed bilateral gynecomasty, extensive leukemic infiltration of typical ATL cells in the mammary glands, and the presence of mammary epithelial cells productively infected with HTLV-I. This is the first report describing invasion of the mammary tissue with HTLV-I-transformed T-cells and HTLV-I-associated breast disease.

Breast↗

PubMed1998

Persistent HTLV-I infection of breast luminal epithelial cells: a role in HTLV transmission?

Human T cell leukemia viruses are predominantly transmitted from mother to child by breastfeeding. Endemic levels of HTLV infection are associated with ethnic groups that have traditionally practised long-term breastfeeding. In the course of long-term lactation, we have found that human milk contains leukocytes and epithelial cells and that mixed primary cultures of these milk cells are susceptible to HTLV-I infection in vitro. We have established and characterized an immortalized line of milk epithelial cells, HTLV-LEC, that are productively infected and transformed with HTLV-I. This is the first reported case of human cells, other than T cells, that are transformed with HTLV-I. Cultures of HTLV-LEC are distinctive because of the synthesis of an extensive extracellular matrix that appears to support in vitro morphogenesis. HTLV-I infection can be transmitted from HTLV-LEC into normal epithelial cells and leukocytes. Our results suggest that infected epithelial cells could be involved in the persistence and transmission of virus infection in HTLV-I carriers.

Animals↗

PubMed1990

Cytokine update.

Explore the source record for details and available documents.

Animals↗

PubMed1989

A role for class I MHC antigens in responses of activated B lymphocytes.

Expression of the H-2 D protein was increased over 10-fold in B cells activated by IL-4 IL-5, IFN-gamma or LPS. Differences in the regulation of H-2 D expression and in growth rates were detected during lymphokine-triggered responses of subpopulations of splenic B cells. The enhancement of H-2 D expression on activated B cells was regulated at the transcriptional level and required synthesis of an intermediate cellular protein(s). B cell growth and differentiation were inhibited by antibodies to the H-2 D Ag suggesting a signaling function for the class I molecules on activated B lymphocytes. In T cells, a similar elevation of H-2 D expression occurred after stimulation with IL-5 or Con A.

Animals↗

PubMed1989

Induction of the H-2 D antigen during B cell activation.

Mitogenic activation causes increased expression of class I Ag of the MHC in mouse B cells. The increased expression was seen in flow cytometry analysis for both K and D in k as well as d haplotypes. A more detailed molecular analysis was carried out for H-2Dd. Increased expression (10- to 20-fold) of the H-2 Dd gene was detected at both protein and messenger RNA levels, and the time course for the accumulation of H-2 Dd protein on the cell surface parallels the increase in the steady-state messenger RNA levels. The increase in H-2 Dd expression in small B cells stimulated with LPS is detectable after 10 h of culture. The present data provide molecular and serologic evidence about alterations in the expression of the H-2 Dd Ag, previously identified as a B cell activation antigen B7.2. Our results indicate a new significance for the function and regulation of the MHC during immune responses, and suggest that the class I molecules may serve some role in the B cell activation process.

Amino Acid Sequence↗

PubMed1987

B cell surface glycoprotein induced during growth response: molecular structure and expression pattern.

We present the molecular characterization of a cell surface antigen, B 7.2, that is expressed on activated B lymphocytes. The BCL1 and CH12 B lymphoma cells express the B 7.2 antigen constitutively. In small resting B cells from spleen, the B 7.2 expression is induced during polyclonal growth in response to mitogenic stimulation. B 7.2 expression also occurs with a significant frequency in cells from fresh lymphoid tissues. The endogenous expression of the B 7.2 antigen is high in spleen and lymph nodes, and is undetectable in the thymus. The B 7.2 antigen is a microheterogeneous 45,000 to 50,000 dalton glycoprotein with a single polypeptide chain, intramolecular S--S bonds, and N-linked glycan moieties. The folded structure of the B 7.2 antigen appears to contain a domain with hydrophilic properties exposed on the cell surface and a hydrophobic segment that may comprise a transmembrane portion. Considering the observed expression pattern and the molecular structure, we speculate that the B 7.2 antigen has a specific function in regulation of B cell activation, perhaps as a receptor for a regulatory ligand or as a ligand recognized by other B or T cells.

Animals↗

PubMedDate not supplied

Molecular characterization of a cloned dolphin mitochondrial genome.

DNA clones have been isolated that span the complete mitochondrial (mt) genome of the dolphin, Cephalorhynchus commersonii. Hybridization experiments with purified primate mtDNA probes have established that there is close resemblance in the general organization of the dolphin mt genome and the terrestrial mammalian mt genomes. Sequences covering 2381 bp of the dolphin mt genome from the major noncoding region, three tRNA genes, and parts of the genes encoding cytochrome b, NADH dehydrogenase subunit 3 (ND3), and 16S rRNA have been compared with corresponding regions from other mammalian genomes. There is a general tendency throughout the sequenced regions for greater similarity between dolphin and bovine mt genomes than between dolphin and rodent or human mt genomes.

Animals↗

PubMedDate not supplied

Mammary epithelial cells support and transfer productive human T-cell lymphotropic virus infections.

OBJECTIVES: To investigate whether luminal and basal human mammary epithelial cells (HMEC) are susceptible to productive infection by human T-cell lymphotropic virus types I and II (HTLV-I and HTLV-II) and whether HTLV infection of breast epithelial cells could contribute to the seeding of milk with HTLV infectivity and support virus transmission from mother to nursing infant. STUDY DESIGN/METHODS: Primary cultures of basal epithelial cells were infected by coculture with mitomycin-C-treated HTLV-producer T-cell lines and HTLV-infected milk epithelial cells, and the transfer of infection was monitored by polymerase chain reaction (PCR) amplification and immunocytochemical staining. RESULTS: Basal mammary epithelial cells were found to be susceptible to HTLV infection and capable of transferring HTLV infection to normal peripheral blood lymphocytes (PBL). CONCLUSIONS: A reservoir for HTLV infectivity could exist in mammary epithelial cells and contribute to the introduction of HTLV infectivity into milk by infecting lymphocytes that traverse the epithelium and by the release of infected epithelial cells, infectious cell fragments, and free virions directly into the milk.

Breast↗

PubMedDate not supplied

Milk-borne transmission of HIV. Characterization of productively infected cells in breast milk and interactions between milk and saliva.

OBJECTIVES: Definition of the cellular constituents of breast milk and infant saliva that are involved in milk-borne transmission of HIV infectivity. STUDY DESIGN/METHODS: Productively infected cells in colostrum and milk of HIV-1-seropositive mothers were identified by in situ hybridization and immunocytochemistry. Additionally, normal cells from mature milk were infected in vitro to determine which cell types were capable of supporting productive HIV-1 infection. Cellular interactions and transfer of HIV-1 in saliva-milk mixtures were studied to monitor the viability of milk cells and the potential for transfer of infectious virus during ingestion of milk. RESULTS: Colostrum and early milk from HIV-1-seropositive mothers contained 0.1% to 1% productivity infected macrophages and T cells. Macrophages and epithelial cells from mature milk were susceptible to productive HIV infection in vitro. When milk was mixed with saliva, milk cells became disrupted or were bound and endocytized by salivary epithelial cells. CONCLUSIONS: Productively infected milk cells may contribute directly to transmission of HIV infectivity in breastfed infants during both early and late lactation. Macrophages are the principal cellular carriers of productive HIV-1 infection in milk. Cellular complexes produced during milk-saliva interactions may play a key role in oral transmission of HIV.

Animals↗