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Biomedical subjects

L Walker

Publications and source records attributed to L Walker.

At least 181 records · Page 10Linked to original sources
PubMed1986

The IgA subclass responses of human lymphocytes to B-cell activators.

The induction of IgA synthesis in normal peripheral blood lymphocytes cultured in the presence of 5 different B-cell activators was studied by immunofluorescence using monoclonal antibodies to the two subclasses. The surface phenotype of normal cells after overnight culture in the absence of mitogen showed a mean ratio IgA1:IgA2 of 2.7:1; cells with cytoplasmic IgA were very rare. Results obtained on different donors after stimulation showed considerable variation; IgA1 was the predominant subclass in Epstein-Barr virus-stimulated cultures, whereas pokeweed mitogen induced a predominantly IgA2 response; cells stimulated with Staphylococcus aureus, Branhamella catarrhalis and lipopolysaccharide and unstimulated cells showed a 1:1 ratio of the subclasses. It is concluded that in this system IgA subclass expression is a function of the activator employed.

Antigens, Surface↗
PubMed1986

Intravesical chemotherapy. Studies on the relationship between pH and cytotoxicity.

The influence of pH on the antitumor activity of drugs used for intravesical chemotherapy was studied. A human continuous cell line derived from a transitional cell carcinoma of the bladder was exposed to 6 drugs (Adriamycin [doxorubicin], cisplatin, epirubicin, epodyl, mitomycin C, and thiotepa) for 1 hour at 11 pH values ranging from 5.2 to 9.7, and cytotoxicity was measured by inhibition of colony formation. pH had a marked influence on drug activity: cisplatin, mitomycin C, and thiotepa were most cytotoxic in acid media, Adriamycin, and epirubicin in alkaline media, while epodyl was the only drug whose cytotoxicity was unaffected by pH. In addition to these in vitro studies, comparisons were made of the pH of urine samples obtained from patients immediately before and at the completion of intravesical chemotherapy. Changes in pH up to a maximum of +/- 1.6 units were observed, although in most cases, values were similar before and after therapy. All the drugs used were acidic in solution, with the exception of thiotepa. It is concluded that by adjusting solvent and urine pH to the optimum value for each drug, the effectiveness of intravesical chemotherapy might be enhanced.

Antineoplastic Agents↗
PubMed1986

Redistribution of protein kinase C during mitogenesis of human B lymphocytes.

G0 human tonsillar B-lymphocytes were stimulated to divide by the polyclonal mitogen Staphylococcus Aureus Cowan strain 1 (SAC) and by the combined use of 12-O-tetradecanoyl phorbol-13-acetate (TPA) and the calcium ionophore ionomycin. The activities of protein kinase C, which requires Ca++ and phospholipid as co-factors, and a proteolytically cleaved form of this enzyme (protein kinase M), which is independent of calcium and phospholipid control, were determined in soluble and particulate fractions obtained from activated B cells. Treatment of G0 B cells with SAC or TPA together with ionomycin caused redistribution of protein kinase C from the soluble to the particulate fraction where the 80,000-Dalton protein kinase C was cleaved to give rise to a 50,000-Dalton form of the kinase which was also found in the cytoplasm. These data suggest that redistribution and proteolytic cleavage of protein kinase C are key signal transduction events in B cell mitogenesis.

B-Lymphocytes↗
PubMed1986

Ligation of the CD23,p45 (BLAST-2,EBVCS) antigen triggers the cell-cycle progression of activated B lymphocytes.

CD23,p45 (BLAST-2,EBVCS) is a 45-kDa lineage-restricted antigen which appears on the surface of human B cells shortly after activation. A monoclonal antibody (MHM6) to CD23,p45, as well as a polyclonal rabbit antibody raised against the purified antigen were found to promote DNA synthesis in purified tonsillar B cells which had been activated with phorbol ester. Interleukin 1, which was not, by itself, stimulatory for either resting or activated B cells, significantly augmented the growth-promoting properties of MHM6. Kinetic studies indicated that while MHM6 exerted its influence in early G1, interleukin 1 acted later in the cycle just prior to the entry of cells into S phase. The findings demonstrate a role for CD23,p45 in triggering the progression of activated B lymphocytes through the G1 phase of the cell cycle. The possibility that this antigen serves as a receptor for a B cell stimulatory factor is discussed.

Animals↗
PubMed1986

Evidence for an association between CD23 and the receptor for a low molecular weight B cell growth factor.

Low molecular weight B cell growth factor (BCGF) and a monoclonal antibody (MHM6) to the 45-kDa, B lineage-restricted, CD23 activation antigen (BLAST-2; EBVCS) were found to be indistinguishable in their biological effects. Individually, both augmented DNA synthesis in activated, but not resting, B lymphocytes while no additional enhancement resulted from using the two agonists in combination. Furthermore, by increasing the expression of Tac, both MHM6 and BCGF promoted activated B cells to respond more vigorously to the late addition of recombinant interleukin 2. The presence of BCGF during B cell activations was found to down-regulate the expression of the CD23 antigen while the coating of activated cells with MHM6 antibody diminished their capacity to absorb BCGF activity. The findings demonstrate that CD23 and a low molecular weight BCGF deliver a comparable growth-promoting signal to activated B cells. A possible relationship between CD23 and the receptor for the low molecular weight BCGF is discussed.

Antibodies, Monoclonal↗
PubMed1986

Autocrine growth of human B lymphocytes: maintained response to autostimulatory factors is the special feature of immortalization by Epstein-Barr virus--a hypothesis.

The autocrine growth profile of human B lymphocytes transformed with Epstein-Barr virus (EBV) was found to comprise three distinct components: a B-cell growth factor (BCGF); an interleukin-1 (IL-1)-like activity; an activity requiring cell-to-cell contact for its action. Observations on the inhibition of the EBV-carrying Daudi lymphoma line by alpha-interferon indicated that loss of response to these autostimulatory factors was underlying growth cessation. Furthermore, a putative receptor for BCGF was found to be down-regulated on B cells stimulated with non-transforming mitogens but constitutively expressed following EBV-transformation. Taken together with recent evidence that normal B cells produce autostimulatory factors, these findings suggest that the special feature of autocrine growth by EBV-immortalized cells is a maintenance of what should normally be a transient phenotype, possibly through deregulation of receptor expression. This hypothesis is discussed.

B-Lymphocytes↗
PubMed1986

Upper aerodigestive neoplasm perpetuated in the nude mouse.

The ability to study and characterize squamous cell cancer of the upper aerodigestive system would be greatly facilitated by an in vivo model. The subsequent opportunity to observe cellular kinetics, membrane antigenicity and hence, potential response to chemotherapy, immunotherapy, radiotherapy, or a combination of these treatment modalities would most likely have early and significant clinical relevance. A multidisciplinary team of basic scientists and clinicians have developed a nude mouse colony for such investigational research. Melanoma and pulmonary squamous and pulmonary adenocarcinoma have been grown and successfully transferred. In addition, head and neck squamous cell carcinoma from multiple sites have also been successfully colonized. We present our experience with this interesting in vivo model and discuss problems in creating a nude mouse colony, techniques of successful tumor inoculation, ongoing maintenance of successful cell lines, and theoretical advantages for potential clinical investigations using this dynamic biologic system.

Adenocarcinoma↗
PubMed1986

Rapid selection of viable transplantable human fetal pancreatic islets by trypan blue exclusion.

A rapid method of separating viable from nonviable human fetal pancreatic islets prior to transplantation is needed to quantify grafted tissue and optimize the possibility of successful treatment of diabetes mellitus in the recipient. After incubation with 0.04% trypan blue in isotonic Krebs-Ringer buffer solution for 15 min, the percentage of islets that excluded trypan blue was found to correlate well with fractional stimulated insulin secretion rates. The incubation procedure did not alter the subsequent insulin secretory capacity of the islets. Trypan blue exclusion rapidly and reliably identifies viable functional islet tissue prior to transplantation.

Cell Separation↗
PubMed1986

Control of human B-lymphocyte replication. I. Characterization of novel activation states that precede the entry of G0 B cells into cycle.

Tonsillar B lymphocytes of a particularly high buoyant density were prepared essentially free of contaminating monocytes and T cells. When exposed to anti-immunoglobulin, such cells initiated the hydrolysis of inositol phospholipids. This provides a postulated 'dual signal' for growth through the liberation of intracellular calcium stores and the activation of protein kinase C. Nevertheless, neither anti-immunoglobulin nor direct agonists of this bifurcating pathway (respectively, calcium ionophore and the phorbol ester TPA) were capable, when used alone, of driving cells out of G0 and into RNA synthesis. All three agents did, however, induce two activation antigens at the surface of G0 B cells, which included CD23, p45 and a lineage-unrestricted antigen identified by the monoclonal antibody BK.19.9. Cells that had been exposed to calcium ionophore, but not those activated with either TPA or anti-immunoglobulin, revealed further change indicated by an increased accessibility of their native DNA for the intercalating dye acridine orange. Cells receiving full mitogenic signals in the form of Staphylococcus aureus Cowan Strain I (SAC) or a combination of TPA and calcium ionophore showed the same initial sequelae but continued to enter the cell cycle and progress through to DNA synthesis. The observations identify two phases in the early activation of human B cells, both in terms of various temporal events, and the signals required to promote each activation state. before entering the proliferative cycle. Thus, the exit of human B cells from G0 appears subject to multiple controls that precede those associated with G1 and later phases of the cell cycle.

Antigens, Surface↗
PubMed1986

Control of human B-lymphocyte replication. II. Transforming Epstein-Barr virus exploits three distinct viral signals to undermine three separate control points in B-cell growth.

Highly purified resting (Go) B lymphocytes were monitored for their response to transforming Epstein-Barr virus (B95-8 strain), to a non-transforming mutant (P3HR-1) containing a deletion in the EBNA-2 coding region, and to inactivated virus of either type. All preparations induced an early appearance of two activation antigens, which included the CD23,p45 ("Blast-2') antigen. Thus, virus binding was sufficient for an initial activation step. Further change required an active viral genome. Infection with the P3HR-1 strain prompted the exit of cells out of Go but led to an arrest in the early G1 phase of the cycle. While initially showing sequels to activation indistinguishable from those observed with P3HR-1 virus, cells infected with B95-8 virus continued through G1 to express late activation antigens, enter S-phase and complete the replicative cycle. The addition of the phorbol ester TPA was found to compensate for the abortive cell cycle entry achieved with the P3HR-1 mutant, but could not supplement the minimal activation observed with inactivated virus. These findings demonstrate that the Epstein-Barr virus undermines three separate control points in the growth cycle of human B lymphocytes, and exploits three distinct viral signals to achieve this end.

Antigens, Viral↗
PubMed1986

The epidermal Langerhans' cell population in psoriasis during topical coal tar therapy.

We have studied the effect on the Langerhans' cell (LC) population of topical 3% coal tar therapy. Biopsies were taken from psoriatic plaques and from controls with no skin disease before and after the application of 3% coal tar for one week; LC were identified by immunofluorescence using monoclonal antibody. LC counts expressed per unit epidermal surface length were similar in untreated psoriasis plaques and in normal skin. Differences in the LC population in paired biopsies from both patients and controls showed considerable variation following coal tar treatment but no consistent effect could be demonstrated.

Antibodies, Monoclonal↗
PubMed1986

Autocrine models of B-lymphocyte growth. II. Interleukin-1 supports the proliferation of transformed lymphoblasts but not the stimulation of resting B cells triggered through their receptors for antigen.

Purified, monocyte-derived interleukin-1 (IL-1) was found to provide growth support for Epstein-Barr virus (EBV) transformed B-lymphocytes seeded at densities below which their own autostimulatory factors were limiting. By contrast, highly purified resting B cells triggered via their receptors for antigen failed to respond to identical preparations of IL-1 by DNA synthesis. That successful priming of the B cells had occurred was evidenced by a transient rise in RNA synthesis and the ability of the cells to respond to T-cell supernatants by DNA synthesis. The findings indicate that while IL-1 might perform an autostimulatory function in B lymphocyte proliferation it is not by itself sufficient to provide growth support for resting B cells activated through their receptors for antigen. The implications of these observations for autocrine models of B-cell growth are discussed.

Antibodies, Anti-Idiotypic↗
PubMed1986

An antigenic study of human plasma cells in normal tissue and in myeloma: identification of a novel plasma cell associated antigen.

A mouse monoclonal antibody named BU11 which detects an antigen strongly expressed on human plasma cells is described. The antibody stains plasma cells in tonsil sections, fresh and cultured plasmacytoid cells from the bone marrow of patients with multiple myeloma and cells of the plasmacytoid cell line RPMI 8226 used as the immunogen. In vitro studies of pokeweed mitogen (PWM) stimulated peripheral blood B cells and Epstein-Barr virus (EBV) stimulated tonsil B cells show that the antigen is present mainly on cells coexpressing the OKT10 antigen and containing cytoplasmic immunoglobulin (cIg). The BU11 antigen is expressed weakly on some normal B cells and is not present on T cells, monocytes or granulocytes. The antigen is of molecular weight 58kD under reducing conditions and is biochemically distinct from previously described plasma cell antigens.

Animals↗