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D W Scott

Publications and source records attributed to D W Scott.

At least 163 records · Page 9Linked to original sources
PubMed1986

Role of self carriers in the immune response and tolerance. X. A lymphoid dendritic-like tumor, P388AD.2, acts as a novel immunogenic carrier for hapten.

Hapten-modified spleen cells, peritoneal exudate cells, and certain lymphoid tumors preferentially induce specific tolerance after i.v. administration. In contrast to these tolerogenic carrier cells, we found that a haptenated lymphoid dendritic-like tumor, P388AD.2, acts as a potent immunogen after i.v. injection. The immunogenicity of P388AD.2 was analyzed by measuring the specific augmentation of plaque-forming cell (PFC) responses when spleen cells from mice previously injected with haptenated tumor cells were challenged in vitro with thymus-independent antigens. Optimal immunization was found to be dependent on cell dose and hapten concentrations. Further studies indicated that P388AD.2 elicited a response which was T cell-dependent and which involved both the so-called Lyb-3,5,7- and Lyb-3,5,7+ B cell populations. Injection of haptenated tumor into different mouse strains suggested that H-2 compatibility was required to prime B cells in vivo, although significant augmentation could also be achieved in allogeneic C57B1/6J mice. The enhanced PFC responses elicited in H-2b mice could not be explained by allo-recognition of class I or II MHC determinants. In toto, these results suggest that P388AD.2 acts as a unique accessory cell for the presentation of hapten-modified self.

Animals↗
PubMed1986

Lymphoma models for B cell activation and tolerance. III. Cell cycle dependence for negative signalling of WEHI-231 B lymphoma cells by anti-mu.

WEHI-231 B lymphoma cells have proven to be a useful model for the regulation of growth of normal B cells by anti-Ig reagents. We previously reported that the growth of these lymphoma cells is inhibited by heterologous or monoclonal anti-mu or anti-kappa reagents. Such cells cease to incorporate thymidine within 24-48 h of exposure to anti-Ig reagents, but are not adversely affected by antibodies directed at either class I or class II histocompatibility antigens. In fact, cell cycle analysis revealed that anti-mu causes a block in the transition of these cells from G1 to S phase. To further study the mechanism of growth inhibition, we have purified lymphoma cells in G1 by centrifugal elutriation, or enriched WEHI-231 cells at the G1/S interface by treatment with hydroxyurea, and followed their progression through the cell cycle in the presence or absence of anti-mu. Our data show that WEHI-231 B lymphoma cells receive a negative signal early in G1, since delayed addition of anti-mu (to late G1 cells) leads to no alteration in cell cycle progression at 24 h, and exposure to anti-mu during S does not alter progress through DNA synthesis and mitosis. Moreover, exposure to anti-mu for only 2 h prevents purified G1 cells from entering their first S phase. The nature of the relevant processes in early G1 is discussed in terms of models of B cell activation and tolerance induction.

Animals↗
PubMed1986

Lymphoma models for B cell activation and tolerance. IV. Growth inhibition by anti-Ig of CH31 and CH33 B lymphoma cells.

CH31 and CH33 are B cell lymphomas whose growth in vitro is inhibited by anti-Ig reagents, including both polyclonal and monoclonal anti-mu antibodies, and an anti-idiotype antiserum. Antibodies against class I or class II major histocompatibility complex antigens do not affect the growth of these cells. Inhibition is dependent on surface Ig cross-linking and does not require ligand binding to Fc receptors. Interestingly, the inhibition of growth by anti-mu is reversed in CH31 (but not CH33) by E. coli lipopolysaccharide. These lymphomas should provide excellent models to study the mechanisms of growth inhibition mediated by surface Ig cross-linking and the pathways of its reversal.

Animals↗
PubMed1986

Radioiodinated surface proteins of rabbit trophectoderm cells.

We have previously used surface iodination to discriminate between the protein patterns of epithelial cell surfaces in uteri of rabbits receptive (Day 6.5) or nonreceptive (Day 4) to nidation (Ricketts et al. 1984). In this paper, we describe application of the same technique to the trophoblastic surface of rabbit blastocysts collected on the same days of pregnancy. Analysis of labelled proteins by polyacrylamide-gel electrophoresis under denaturing conditions did not reveal qualitative differences between the two days of pregnancy. Scanning densitometry was used to quantitate the area under each protein peak on an autoradiogram; these areas were used as variables in statistical analysis of the protein pattern of individual animals. Quantitative differences between the protein patterns of the two surfaces were detected by canonical variate analysis of the pattern of relative areas of labelled protein peaks. In proteins separated on 7.5% gels, this statistical analysis correctly assigned blastocysts from 8 out of 10 animals to one of two groups according to day of pregnancy. The discrimination was not statistically significant, however, in protein patterns on 12.5% gels, used to give better separation in the lower range of molecular weights. The same analysis in the uterus unequivocally separated the surface iodination patterns from these same days of pregnancy. Thus the changes detected by surface iodination appear to be less pronounced on the trophectoderm than on the uterine epithelium in relation to the time of ovoimplantation.

Animals↗
PubMed1985

Three classes of signalling molecules on B-cell membranes.

The question of whether surface immunoglobulin and Ia molecules have a signalling function in helper T cell-dependent activation of B cells has been evaluated. Two sources of B cells have been used, one a purified population of hapten-binding B cells, the other a B-cell lymphoma, CH12, with known antigen specificity. Evidence is presented that both immunoglobulin and Ia molecules are receptors actively involved in the initial activation of resting B cells. Nevertheless, the requirements for ligand binding to either receptor can be bypassed under appropriate conditions, and the implications of this result for the function of these molecules is discussed. With respect to B-cell Ia, the authors present data that demonstrate two distinct functions of this molecule, one as a restricting element for T-cell activation, the second as a signalling receptor for B-cell excitation. On the CH12 surface, the I-A molecule fulfills the former function, but T-cell interactions with I-A fail to result in B-cell stimulation, suggesting that B-cell Ia may limit helper T cell-B cell interactions. We suggest that the binding of antigen surface immunoglobulin and binding of helper T-cell receptors to the appropriate Ia molecule(s) results in the activation of genes that encode for a third class of membrane B-cell receptors, those that bind B-cell stimulating factors.

Animals↗
PubMed1985

Lymphoma models for B-cell activation and tolerance. II. Growth inhibition by anti-mu of WEHI-231 and the selection and properties of resistant mutants.

Regulation of the growth of murine B-cell lymphomas has been used as a model for tolerance induction. The inhibition by anti-immunoglobulin reagents of the growth of WEHI-231 and several variant clones has now been studied. The parental line is exquisitely sensitive to growth inhibition by heterologous or monoclonal anti-mu or anti-k reagents and ceases to incorporate thymidine within 24-48 hr of exposure to anti-immunoglobulin reagents. Growth inhibition is initially reversible, but prolonged exposure to anti-mu results in cell death. This inhibition is specific for immunoglobulin light and heavy chains since growth is not inhibited by antibodies directed at either class I or class II histocompatibility antigens. In order to study the mechanism of growth inhibition, we have mutagenized WEHI-231 with ethylmethane sulfonate and cloned the surviving colonies in the presence of anti-mu. Such variants, which have been repeatedly recloned, are able to grow normally in the presence of anti-mu up to 100 micrograms/ml. These "resistant" clones, while expressing amounts of surface IgM similar to that observed on WEHI-231, do not differ markedly in their ability to cap their immunoglobulin receptors compared to the parental line but appear to have lost class II antigens. Cell cycle analysis revealed that anti-mu causes a block in the transition of WEHI-231 from G1 to S phase. The relevance of these processes to models of B-cell tolerance induction are discussed.

Animals↗
PubMed1985

Asperger's syndrome and non-verbal communication: a pilot study.

The study investigated the ability of 10 patients with Asperger's syndrome to recognize and produce non-verbal aspects of facial and spoken (e.g. vocal intonation) communication by use of photographs, audiotape and videotape. It also aimed to establish materials to differentiate individuals with this condition from a comparable non-Asperger group. Asperger subjects tended to be poorer than comparable patients on all subtests.

Adolescent↗
PubMed1985

Lymphoma models for B cell activation and tolerance. I. Conditions for the anti-mu-dependent stimulation of growth in NBL, a nude B cell lymphoma.

NBL is a spontaneous B cell lymphoma that originated in NIH Swiss nude mouse, and has been maintained as an in vitro line for 4 yr in our laboratory. It is surface IgM positive and expresses several B cell markers including Fc receptors, as well as Ly-1. Although clones of NBL will grow in serum-containing medium, this cell line enters a quiescent state in serum-free culture. However, in the presence of affinity-purified or monoclonal anti-mu reagents, NBL increases its rate of proliferation as measured by thymidine incorporation or in absolute cell numbers. This stimulation is specific for mu-chain, because it does not occur with anti-beta 2 microglobulin, irrelevant nonbinding antibodies, or with monoclonal anti-B cell lineage markers. Bivalent anti-mu is required, and no consistent Fc-mediated inhibition of growth has been detected. Stimulation of NBL occurs optimally at critical cell densities (greater than 3 X 10(3)/well) in the absence of serum. Therefore, we reasoned that NBL either produced or was receptive to known B cell growth factors. Although no classic IL 1 was detected in NBL supernatants, some BCGF-I-like activity was found. Finally, in the presence of LPS, both spontaneous and anti-mu-stimulated NBL growth was inhibited, a result suggesting maturation of this lymphoma. These results suggest that NBL represents an excellent model to study the growth and differentiation of B cell subsets.

Animals↗
PubMed1985

Evaluation of a pump in enteral tube feeding in terms of patient and staff acceptance: a retrospective study.

A retrospective study of 39 patients fed via an enteral tube was carried out using data from patients records. An enteral feeding pump was available for all patients. Its use was evaluated in terms of patient and staff acceptance of the technique. The pump was shown to be particularly suited to patients following gastrointestinal surgery and trauma in whom tube feeding might be expected to produce gastrointestinal side-effects. Patients with lower nutritional requirements and without gastrointestinal trauma do not require such accurate flow control and for non-clinical reasons an alternative technique such as gravity drip feed or bolus feeding may be preferred. The conclusions which can be drawn from a study of this nature are limited but it does draw attention to the importance of considering, in addition to the expected clinical tolerance, the acceptance by patient and staff of the technique for the individual.

Attitude↗
PubMed1984

Radioiodinated surface proteins of separated cell types from rabbit endometrium in relation to the time of implantation.

To investigate changes in surface proteins of uterine cells in relation to the time of implantation, epithelial and stromal cells were isolated from rabbit endometrium and maintained in primary culture for 3 days. Surface-iodination of intact cells was carried out before and after culture, using immobilized Iodogen catalyst. The labeled proteins were analyzed by polyacrylamide gel electrophoresis, followed by autoradiography; peak areas were quantitated by scanning densitometry. Different gestational ages showed no marked qualitative differences in the surface-iodination patterns either of epithelial or stromal cells before or after culture. Quantitative differences between the surface-iodination pattern of epithelial cells from days 4 to 6.5 of pregnancy were revealed by canonical variate analysis of labeled peak areas. Values for individual rabbits clustered according to gestational age, with significant (p less than 0.05) separation of the clusters, although the discrimination was less pronounced for cultured than for freshly isolated cells. Changes involving increases in labeling of a protein of 38000 Mr in fresh cells, and decreases in a protein of 42000 Mr in cultured cells, were evident between day 4 and day 6.5. Thus changes in the surface-labeling pattern of uterine epithelial cells in relation to the time of receptivity for ovoimplantation can be distinguished. The functional significance of these changes remains to be elucidated.

Animals↗
PubMed1984

Cloning of B cells from autoimmune MRL-lpr/lpr and MRL.xid mice.

The relationship between colony formation (cloning) of B cells and their activation in murine autoimmunity was investigated in MRL-lpr/lpr and MRL.xid mice. Cells from MRL-lpr/lpr mice showed similar requirements for in vitro growth as normal CBA/J and BALB/c cells, with maximal colony formation in the presence of the supporting factors lipopolysaccharide and sheep red blood cells. The frequency of colony-forming cells from MRL-lpr/lpr spleens or hapten-specific B-cell preparations was slightly greater than the two normal control strains, with this difference significant only for a comparison of BALB/c and MRL-lpr/lpr spleens. In contrast, MRL-lpr/lpr mice bearing the xid gene for B-cell immunodeficiency (MRL.xid) had markedly reduced B-cell colony formation. These mice nevertheless expressed anti-DNA antibodies, although at levels reduced from that of MRL-lpr/lpr controls. These results indicate that enhanced in vitro colony formation need not accompany B-cell hyperactivity in murine autoimmune disease and that autoantibody production can occur in mice with impairment in this growth property.

Animals↗
PubMed1984

Major histocompatibility complex-restricted and unrestricted interactions in the T cell-dependent activation of hapten-binding B cells.

The requirements for linked recognition and major histocompatibility complex-restricted interactions in helper T cell-dependent activation of purified unprimed and primed hapten-binding B cells have been investigated. The activation of unprimed hapten-binding B cells required specific antigen and restricted interactions between helper T cells and B cells. As expected, specific hapten-carrier conjugates were essential for the activation of B cells at low antigen doses. Interestingly, however, supraoptimal concentrations (125 micrograms/ml) of carrier protein alone could substitute for specific conjugates in the activation of unprimed B cells. The requirement for restricted helper T cell-B interactions was unchanged under these conditions. These results are discussed in terms of the signalling requirements for B cell activation. In contrast to the results using hapten-specific B cells from unprimed mice, the further stimulation of B cells prepared from mice primed 5 to 7 days earlier with immunogenic forms of the hapten was limited only by the requirements for helper T cell activation. The transition in the activation properties of B cells following in vivo stimulation was not solely a result of the binding of B cell membrane immunoglobulin to specific antigen, since the interaction of unprimed B cells with hapten during their purification, even for extended periods of time, did not alter the requirements for their further stimulation. These results demonstrate that the recent antigenic experience of B cells determines their activation state which, in turn, dictates the further requirements for helper T cell function in B cell stimulation. This implies that specificity of the immune response is determined in the early stages of B cell activation.

Animals↗
PubMed1984

Modified-self-induced modulation of the immune response to herpes simplex virus: effect on antibody formation, cytotoxic T lymphocyte induction, and survival.

C3H/HeJ mice were injected i.v. with soluble herpes simplex virus (HSV) envelope antigens coupled to syngeneic splenocytes 7 days before challenge i.p. with either soluble HSV antigens in complete Freund's adjuvant or infectious HSV. Fourteen days post challenge, and anti-HSV antibody hyporesponsiveness was observed in the HSV modified-self pretreated animals that was 50% or less than the control response. Both forms of HSV challenge were equally effective. This unresponsiveness was specific for HSV when compared with a concomitant response to chicken red blood cell (CRBC) challenge. Challenge with infectious HSV afforded us the opportunity to investigate the effect of HSV modified-self pretreatment on the induction of HSV-specific cytotoxic T lymphocytes (CTL). In vitro restimulation of in vivo-primed splenocytes with infectious HSV generated HSV-specific CTL. The degree of HSV-specific CTL response was found to be variable in animals that received the HSV modified-self pretreatment with respect to control animals. Survival was significantly greater in HSV modified-self pretreated mice after infectious HSV challenge than in control animals.

Animals↗