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Biomedical subjects

A M Lewis

Publications and source records attributed to A M Lewis.

At least 55 records · Page 3Linked to original sources
PubMed1994

Imaging of cortical spreading depression by EIT: implications for localization of epileptic foci.

Severe epileptics may require curative neurosurgery. Sometimes focus localization requires recording with electrodes inserted deep into the brain, which may cause death or permanent neurological damage. Since epileptic seizures are associated with marked changes in cerebral impedance, we propose that EIT with sub-dural electrodes (inserted between the brain and skull) could provide a superior and less dangerous method for the localization of epileptic foci. The purpose of these experiments was to determine whether EIT could be used to localize the origin of seizure activity. In terms of impedance characteristics, an appropriate model is cortical spreading depression in the animal brain. Six rabbits were anaesthetized and paralysed and the brain exposed. EIT images and DC potentials were recorded from an array of 16 electrodes on the brain during cortical spreading depression induced by DC stimulus. Cortical spreading depression could be localized by EIT with an accuracy of 8.7% +/- 6.4% (mean +/- SD) of electrode array diameter. The errors in localization appeared to be distributed randomly. In a phantom of similar geometry, the error was 5% after correction for a systematic component. Results are sufficiently encouraging that we intend to extend this study to human patients.

Animals↗
PubMed1992

Stimulation of protein synthesis and expansion of pig blastocysts by insulin in vitro.

Present evidence indicates that insulin may act as a growth factor during preimplantation development. This hypothesis has been tested on pig blastocysts by determining the effect of insulin on protein synthesis and blastocyst expansion over 24 h. Blastocysts were collected from superovulated gilts or sows on Day 5 or 6 and incubated overnight in a modified BMOC2 medium. Those that were cultured with 1.7 nM insulin had 14% larger radii, and were 36% more active in their incorporation of [3H]leucine (protein synthesis) than those that had been cultured in non-supplemented medium. There was a significant linear correlation between the rate of protein synthesis and the radius of blastocysts when all blastocysts and only those cultured with insulin were examined, but the correlation for the blastocysts in non-supplemented medium was just outside statistical significance. The regression coefficient for the insulin-treated blastocysts was 132% of that for blastocysts cultured in unsupplemented medium; this suggests that insulin increased the size of blastocysts and the rate of protein synthesis per unit size. The results indicate that pig blastocysts respond to physiological levels of insulin in similar fashion to those of mice and cattle, supporting the hypothesis that insulin may act as a general embryonic growth factor. Because of the cross reaction between the insulin receptor and the ligands, insulin and insulin-like growth factor 1 (IGF-1), the results also suggest that IGF-1, reported to be present in pig uterine fluid, could be involved in this stimulation in utero.

Animals↗
PubMed1992

Driving adenovirus type 12-transformed BALB/c mouse cells to express high levels of class I major histocompatibility complex proteins enhances, rather than abrogates, their tumorigenicity.

The tumorigenicity of adenovirus type 12 (Ad12)-transformed cells has been attributed to the low levels of class I major histocompatibility complex (MHC) protein expression by these cells. These levels of class I proteins are thought to be below the threshold critical for cytotoxic T-lymphocyte recognition, a process that may be involved in tumor cell immunosurveillance. We have used gene transfer experiments to investigate the role played by class I protein expression in the tumorigenicity of Ad12-transformed BALB/c mouse cells in naive, syngeneic adult mice. Our Ad12-transformed mouse cells were tumorigenic in adult mice and were similar to other Ad12-transformed mammalian cells in that they expressed low levels of class I MHC mRNA and cell surface proteins. Despite these low levels of expression, the cells were highly immunogenic in syngeneic mice and were rejected as allografts by allogeneic mice. Transfection of genomic H-2Dd or H-2Ld fragments into these cells produced a variety of cell clones that expressed increased levels of cell surface class I proteins. These cells expressing high levels of class I protein were up to 16-fold more tumorigenic than the parental cells in syngeneic adult mice. Thus, by quantitative assays, the tumorigenicity of Ad12-transformed BALB/c mouse cells is not functionally related to the low levels of class I MHC proteins they express. The increased tumorigenicity expressed by H-2Dd- and H-2Ld-transfected cells was not detected in BALB/c nu/nu mice, suggesting that a thymus-dependent mechanism that is not mediated by evasion of cytotoxic T-lymphocyte recognition could contribute to the difference in tumorigenicity of Ad12-transformed BALB/c mouse cells that express low and high levels of class I MHC proteins.

Adenoviridae Infections↗
PubMed1992

Characterization of glutamine uptake in mouse two-cell embryos and blastocysts.

Mouse two-cell embryos and blastocysts take up [3H]glutamine in vitro at a constant rate for at least 15 min, depending on the concentration of glutamine and developmental stage of the embryo. Uptake by two-cell embryos can be resolved into two saturable components. The major contributing system is Na+ independent, inhibited by alanine, methionine, 2-amino-2-norbornanecarboxylic acid (BCH) or leucine and has a Km of 3856 +/- 672 mumols l-1 and Vmax of 436 +/- 58 fmol per embryo per 10 min. These features are characteristics of the ubiquitous system L transporter. The second component is Na+ dependent with Km of 1064 +/- 914 mumols l-1 and Vmax 107 +/- 47 fmol per embryo per 10 min. Similar Vmax and inhibition of this component by glycine suggest a low reactivity with the gly-system. Blastocyst uptake of glutamine is mainly by a Na(+)-dependent saturable mechanism with Km of 524 +/- 75 mumols l-1 and Vmax of 1264 +/- 101 fmol per embryo per 10 min which is inhibited by alanine, isoleucine, leucine and BCH, features characteristic of the system B0,+. The increase in uptake capacity as a consequence of the appearance of the system B0,+ may be related to increased metabolic requirements for glutamine, in the rapidly expanding blastocyst.

Animals↗
PubMed1991

E1A oncogene induction of cytolytic susceptibility eliminates sarcoma cell tumorigenicity.

The manner in which oncogenes influence tumorigenicity beyond their ability to immortalize cells is uncertain. We tested the hypothesis that, in addition to subverting cellular growth controls, oncogenes can actively determine tumor-inducing capacity by affecting neoplastic cell susceptibility to destruction by the host cellular immune response. The adenovirus type 5 E1A oncogene, which induces susceptibility to lysis by natural killer cells and encodes epitopes recognized by cytotoxic T lymphocytes, was transfected into highly tumorigenic sarcoma cells. E1A expression in these sarcoma cells eliminated their tumorigenicity in recipients with natural killer cell activity that was competent to lyse these E1A-positive targets. Thymus-dependent responses were not required for tumor rejection. These results indicate that oncogene-regulated cellular pathways that affect neoplastic cell susceptibility to natural killer cell lytic mechanisms may influence tumor development in the immunocompetent host.

Adenovirus Early Proteins↗
PubMed1990

Syrian hamsters express diverse MHC class I gene products.

MHC class I glycoproteins are highly diverse in most species. The Syrian hamster has long been thought to express monomorphic MHC class I molecules and thus be an exception to this rule. Here we show that Syrian hamsters express diverse MHC class I gene products. The nucleotide sequences of the alpha 1 and alpha-2 domains of classical Syrian hamster MHC class I molecules are highly variable and show evidence of having been under selective pressures at their Ag recognition sites. Interestingly, none of the Syrian hamster class I genes was closely related to their counterparts in the mouse. These observations suggest that Syrian hamsters in the wild may express diverse MHC class I molecules.

Animals↗
PubMed1990

Expression of human immunodeficiency virus long terminal repeat in the human promonocyte cell line U937: effect of endotoxin and cytokines.

Phagocytic macrophages are known to support noncytopathic, chronic infections of human immunodeficiency virus (HIV). Regulation of viral replication in such cells with either chronic low-grade or latent HIV infection is probably influenced by both viral and cellular factors acting on the viral long terminal repeat (LTR). This study identifies naturally occurring biological response modifiers which are able to affect the HIV-LTR linked to the chloramphenicol acetyl transferase (LTR-CAT) gene in a stable transfection of the human promonocyte cell line, U937, in the absence of other viral proteins. In this model system, endotoxin lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) are able to independently stimulate expression of LTR-CAT. Granulocyte/macrophage-colony-stimulating factor can enhance the effect of TNF-alpha or LPS, but other cytokines tested had minimal or no effect on LTR-CAT. In addition to effects on cellular susceptibility and immune function, the ability of naturally occurring factors to affect HIV-LTR in its integrated state may have particular relevance to progression of active disease from latent infection.

Biological Factors↗
PubMed1990

Use of bacteriology in anorectal sepsis as an indicator of anal fistula: experience in a distinct general hospital.

The bacteriology of anorectal sepsis in a district general hospital has been reviewed to see whether the information gained helped patient management. Forty-six patients with anorectal sepsis were reviewed, underlying fistulas were identified in nine patients (19.5%). Bacteroides species were not routinely subtyped in the department. It was found that isolation of unspecified Bacteroides species was not helpful in identifying those patients with underlying fistulas. Unless subtyping of Bacteroides species is specifically requested, pus from anorectal sepsis should not routinely be sent for bacteriology.

Abscess↗
PubMed1989

Biochemical properties of media conditioned by simian virus 40-induced hamster tumor cells: correlation with distinct cell phenotypes but not with oncogenicity.

Hamster cells, transformed in vitro by SV40, have been reported to secrete an unidentified factor(s) that inhibits thymidine uptake (TU) by various normal cell types, including activated lymphocytes. It has been postulated that this apparent antiproliferative effect may play an in vivo role in the high tumorigenic capacity of SV40-transformed hamster cells. In keeping with this hypothesis, Adenovirus type 2-transformed hamster cells, which are only weakly tumorigenic, do not inhibit TU by indicator cells in vitro. To study the biological relevance of this phenomenon, we assayed 11 cell lines derived from different fibrosarcomas, induced in Syrian hamsters by SV40, for their ability to inhibit TU by normal rabbit kidney indicator cells. In contrast to cells transformed in vitro by SV40, media conditioned by 6 of 11 tumor-derived cell lines did not inhibit TU. Our results do not support the hypothesis that an antiproliferative factor secreted by SV40-transformed cells promotes the tumor-inducing capacity of these cells. Furthermore, inhibition of TU does not appear to be due to the production of a specific antimitotic peptide, but rather to other biochemical properties of the media conditioned by transformed cells. Finally, these biochemical properties do appear to correlate with specific morphological and growth characteristics of the tumor cells, but probably as an effect and not a cause.

Animals↗
PubMed1989

Characterization of hamster tumors induced by simian virus 40 small t deletion mutants as true histiocytic lymphomas.

Random bred Syrian hamsters given s.c. injections of SV40 small t deletion mutants dl883, dl884, and dl890 rapidly develop reticulum cell sarcomas in the abdominal cavity in addition to slowly developing s.c. fibrosarcomas at the site of virus inoculation. Injection of wild type SV40 s.c. induces only fibrosarcomas at the site of inoculation. In an attempt to understand why mutations in the SV40 small t gene should lead to this difference in tumor-inducing capacity in hamsters, we studied cells from 12 abdominal reticulum cell sarcomas which were induced by the s.c. injection of SV40 mutants. Morphological and functional analyses indicate that these tumor cells are derived from MAC-2+ macrophages. They are highly granulated, vacuolated, and multinucleated, and they generally adhere to glass and plastic. In addition, they (a) phagocytose latex beads; (b) express high levels of class II major histocompatibility complex antigens; (c) contain beta-glucuronidase, acid phosphatase, and fluoride-inhibited nonspecific esterase; (d) contain lysozyme and fibronectin; and (e) express cell surface MAC-2 antigens. Thus, the small t deletions in the SV40 genome appear to permit the virus to transform cells that are distant from the site of virus inoculation; at this distant site, the cells transformed are of a specific lineage, MAC-2+ peritoneal macrophages. This specific tropism may reflect a unique characteristic of MAC-2+ cells or their precursors that renders these cells susceptible to SV40 mutants which are otherwise restricted in the range of cells that they can transform.

Abdominal Neoplasms↗
PubMed1988

In vivo evolution of adenovirus 2-transformed cell virulence associated with altered E1A gene function.

Neoplastic cell populations may evolve to a state of higher virulence in immunocompetent hosts. Transforming gene involvement in this process of tumor progression was evaluated using adenovirus type 2 (Ad2)-transformed hamster cells that are highly susceptible to destruction by natural killer cells and activated macrophages, due to Ad E1A gene function, and are nontumorigenic in immunocompetent animals. Cells selected for increased tumorigenicity retained parental cell patterns of viral gene integration and methylation and expressed Ad2 E1A proteins but exhibited altered E1A function evidenced by decreased susceptibility to killer cell-mediated lysis and inability to support E1A(-) mutant virus replication. The data suggest that an interruption in cellular pathways of E1A expression may result in increased transformed cell virulence.

Adenoviridae↗
PubMed1988

A test of the air-seeding hypothesis using sphagnum hyalocysts.

"Air-seeding" is a proposed mechanism for the initiation of water stress embolism in dead plant cells. During air-seeding, external air is drawn into the lumen of a dead plant cell through a pore or crack in the cell wall. The resulting bubble may expand to fill the lumen, thus embolizing the cell. The data presented confirm that Sphagnum hyalocysts can embolize by air-seeding when the pressure difference across the air-water meniscus is given by DeltaP = 0.3/D (derived from the capillary equation), where DeltaP is the pressure difference across the meniscus (megapascal), and D is the diameter (micrometer) of the pore through which the air bubble enters.

Journal Article↗