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D M Jacobs

Publications and source records attributed to D M Jacobs.

108 records · Page 6Linked to original sources
PubMed1979

Synergy between T cell-replacing factor and bacterial lipopolysaccharides (LPS) in the primary antibody response in vitro: a model for lipopolysaccharide adjuvant action.

Unfractionated spleen cells, B cells from normal mice, and nu/nu spleen cells respond to the addition of bacterial lipopolysaccharide (LPS) and T-cell-replacing factor (TRF) by production of plaque-forming cells (PFC) in excess of the number expected from the addition of LPS and TRF separately. This synergistic activity is dependent on the presence of the antigen, SRBC. Supernatants of both allogeneic spleen cell mixtures and spleen cells cultured with Con A are effective and synergize best at concentrations suboptimal for their ability to act as TRF alone. Culture supernatants of unstimulated normal or fractionated cell populations are ineffective. Synergy is not dependent on the presence of macrophages in the cultures. Purified LPS free from active contaminants, as well as commercially available LPS, show synergy with TRF. Synergy was seen when TRF was added at initiation of culture or 24 hr later. It is suggested that synergy is the equivalent of LPS adjuvant activity, that the role of T cells in LPS adjuvanticity is that of a conventional cooperating cell, and the LPS acts as an adjuvant by inducing B cells to become more sensitive to T cell helper factors.

Adjuvants, Immunologic↗
PubMed1978

Modulation of immune response by bacterial lipopolysaccharide (LPS): cellular basis of stimulatory and inhibitory effects of LPS on the in vitro IgM antibody response to a T-dependent antigen.

The role of thymus-derived lymphocytes (T cells) in LPS modulation of T cell-dependent antibody responses has been investigated. We have assessed the effect of LPS on the primary anti-TNP response to TNP-SRBC of cultures of whole spleen cells or T cell-depleted spleen cells that were supplemented with various subpopulations of carrier-primed (SRBC) spleen cells. The TNP-PFC response was enhanced in the presence of irradiated SRBC-primed spleen cells by addition of 0.16 to 20 microgram/ml LPS, but inhibition was observed when irradiation of primed cells was omitted. Enhancement but no inhibition occurred when added primed cells were first passed through a nylon wool column. LPS-mediated enhancement was dependent on a T cell in the primed population. These results suggest that LPS modulation of antibody synthesis is dependent on two populations of antigen-specific cells that have opposing effects on B cell responses to a T-dependent antigen: a helper cell that is irradiation resistant, nonadherent to nylon wool, and sensitive to anti-T cell serum, and a suppressor cell that is irradiation sensitive and adherent to nylon wool.

Animals↗
PubMed1978

Modulation of immune response by bacterial lipopolysaccharide (LPS): multifocal effects of LPS-induced suppression of the primary antibody response to a T-dependent antigen.

Spleen cells from mice injected with 2 to 50 microgram bacterial lipopolysaccharide (LPS) have a reduced capacity to make an antibody response in vitro to trinitrophenylated sheep erythrocytes (TNP-SRBC) when tested 1 to 7 days later. Recovery is gradual, and these cells are full functional 2 weeks after in vivo LPS treatment. Unresponsiveness resides in the nonadherent splenic cell populations, and can be shown to have a suppressive cell component, which is irradiation sensitive and has somme characteristics of a thymus-derived lymphocyte (T cell). In addition, neither bone marrow-derived lymphocytes (B cells) nor T cells in the spleens of LPS-treated mice are functionally normal in their abilities to cooperate during an antibody response in vitro. LPS-B cells cooperated poorly with nylon wool-enriched T cells from normal mice but cooperated well with irradiated carrier-primed T cells or nylon wool-purified splenic T cells from carrier-primed mice. LPS-T cells have a reduced capacity to interact with normal B cells and appear to contain a suppressor cell component. These results indicate that the effects of exposure of immunocompetent cells to LPS are multifocal and can include suppression as well as stimulation of antibody formation.

Animals↗
PubMed1977

Inhibition of the mitogenic response to lipopolysaccharide (LPS) in mouse spleen cells by polymyxin B.

The addition of low doses of the cationic polypeptide antibiotic, polymyxin B (PB), to cultures of mouse spleen cells inhibits lipopolysaccharide-(LPS) induced DNA synthesis but not that stimulated by PPD, PHA, or Con A. Inhibition is stoichiometric; the mitogenic response is suppressed by 50% at a weight ratio of PB:LPS of 0.055 to 1. Furthermore, PB-LPS complexes have a much reduced mitogenic capacity. These complexes inhibit the mitogenic response of spleen cells to unmodified LPS but not to PPD, Con A, or PHA. The inhibitory activity of PB is less effective when added after LPS is mixed with responding cells, achieving 50% inhibition when addition is made at 4 to 6 hr. Time course experiments indicate that partial inhibition is a reflection of a lower rate of DNA synthesis. Thus, PB inhibition of LPS mitogenesis apparently occurs as a result of formation of PB-LPS complexes with reduced mitogenic capacity. Specific inhibition by the complexes of mitogenesis induced by native LPS suggests that the inactive complex may bind to B cells but is unable to trigger them.

Animals↗
PubMed1976

Isolation of a lipid A bound polypeptide responsible for "LPS-initiated" mitogenesis of C3H/HeJ spleen cells.

The experiments by Sultzer and Nilsson (1), and later by Watson and Riblet (2), established that spleen cells from the C3H/HeJ strain of mouse were refractory to the mitogenic effects of bacterial lipopolysaccharides (LPS). More recently, however, experiments from our laboratory (3) demonstrated that spleen cells from C3H/HeJ mice were in fact responsive to some preparations of LPS but not to others, and that the method of extraction played a critical role in determining activity. In particular, preparations of LPS prepared by extraction with aqueous butanol had potent mitogenic activity. Our data showed that the mitogenic activity of such positive preparations of LPS coisolated with the LPS during gel filtration chromatography and subsequent equilibrium banding on CsCl. In addition, lipid A isolated from positive preparations of LPS was also capable of stimulating C3H/HeJ spleen cells. Taken together, these experiments provided rather convincing data that it was the LPS (in particular the lipid A) itself, or some contaminant very tightly bound to the lipid A, which was responsible for its biological activity. We further demonstrated that treatment of positive preparations of LPS with hot phenol rendered such preparations nonmitogenic for C3H/HeJ spleens, yet activity for other strains was only moderately decreased. These experiments would suggest either that the phenol treatment chemically alters the lipid A region of the LPS molecule or that such treatment removes the putative tightly bound contaminant responsible for C3H/HeJ mitogenesis. In the experiments reported here, we have explored in greater detail the role of lipid A in the stimulation of C3H/HeJ spleen cells. For these experiments we have utilized our earlier observations that the antibiotic polymyxin B forms a highly stable molecular complex with the lipid A region of LPS (4), and that such polymyxin B-LPS complexes are unable to mitogenically stimulate B lymphocytes (5). In addition, we have attempted to distinguish between the two potential modes of action of phenol on LPS, namely, the chemical alteration of the lipid A or the removal of a tightly bound contaminant by phenol treatment. The results of the experiments we report here support the interpretation that mitogenic activity of positive preparations of LPS is associated with a low mol wt phenol soluble polypeptide of approximately 10,000 mol wt. After partial purification, this polypeptide intitiates a significant mitogenic response at concentrations as low as 10 mug/ml. We conclude that the C3H/HeJ strain of mouse is a true nonresponder to the stimulatory effects of the lipid A region of LPS.

Animals↗
PubMed1975

Stimulation of a T-independent primary anti-hapten response in vitro by TNP-lipopolysaccharide (TNP-LPS).

The trinitrophenyl hapten (TNP) has been covalently conjugated to bacterial lipopolysaccharides (LPS) to give TNP-LPS. The site of attachment has been suggested to be in the core polysaccharide and lipid A region of the molecule and approximately 2.4 hapten molecules are bound per monomer LPS molecule. The TNP-LPS has been demonstrated to be immunogenic in vitro at very low concentration. This antigen has further been shown to initiate a T-independent TNP-PFC response. The immunogenicity of TNP-LPS is abrogated by mild alkaline hydrolysis, suggesting a requirement for intact lipid A in the initiation of an immune respose at the very low concentrations of antigen used.

Alkalies↗
PubMed1975

Effects of concanavalin A on the in vitro responses of mouse spleen cells to T-dependent and T-independent antigens.

?The stimulatory and inhibitory effects of concanavalin A (Con A) on the in vitro primary immune responses to a T-dependent antigen, sheep erythrocytes (SRBC) and a T-independent antigen, TNP-lipopolysaccharide (TNP-LPS) have been studied. Inhibition of the response to both antigens was optimal when 2 mug Con A were added at the initiation of the culture period. The response to SRBC was considerably enhanced by the addition of Con A 24 hr later. In contrast, this late addition did not stimulate the TNP-LPS response and often inhibited it. Inhibition of the TNP-LPS response required the participation of T cells since it was not observed in cells from adult thymectomized irradiated bone marrow-reconstituted (ATXBM) mice. The response to TNP-LPS was somewhat enhanced in ATXBM cells, but the degree of enhancement was strikingly less than that observed for SRBC. LPS per se did not block the stimulatory effect of Con A on the SRBC response, and was observed to act synergistically with this lectin. None of the Con A effects observed required the participation of adherent cells. These observations are consistent with a model in which different subpopulations of T cells are responsible for the inhibitory and stimulatory effects. They further suggest that the Con A inhibitory activity acts via a T cell to inhibit directly the B cell response to antigen.

Animals↗
PubMed1975

Structural and genetic basis of the in vivo immune response to TNP-LPS.

TNP-lipopolysaccharide (TNP-LPS) is a potent T-independent antigen in vivo, inducing a TNP-PFC response in T-depleted animals. The structural integrity of the lipid A-KDO portion of the LPS carrier molecule appears to be required since the haptenated LPS from Salmonella minnesota Re595 is immunogenic whereas the haptenated derivative of base hydrolyzed LPS is not. The immune response is not associated with any of the common histocompatiblity types, but does depend on the ability of the host strain to respond to LPS. C3H/HeJ mice are not killed by low doses of LPS and give a poor PFC response to TNP-LPS. Lethality and immunogenicity are dominant responses in hybrids of C3H/HeJ and responder mice. The structural and genetic requirements for the response to TNP-LPS suggest an active role for the carrier in the immunogenicity of this T-independent antigen.

Animals↗
PubMedDate not supplied

The relationship of hemorrhoids to portal hypertension.

Records of 188 patients with documented portal hypertension were reviewed to determine the incidence of hemorrhoids as well as bleeding complications associated with this condition. The incidence of hemorrhoids among these patients was not increased compared to the normal population. Six of the patients with portal hypertension did, however, bleed massively from hemorrhoids. Elevated portal venous pressure is an important factor in those patients having severe hemorrhoidal bleeding. The presence of coagulation defects may also be of considerable importance.

Adult↗
PubMedDate not supplied

Structural features of binding of lipopolysaccharides to murine lymphocytes.

A sensitive hapten-sandwich immunofluorescence technique was used to examine binding of lipopolysaccharide (LPS) at the single-cell level. The structural features governing such binding to murine lymphocytes were investigated by evaluating LPS binding in the presence of a variety of charged molecules and after different target-cell treatments. Polymyxin B, the positively charged proteins egg-white lysozyme and protamine chloride, and the polyanion dextran sulfate inhibited LPS binding to murine lymphocytes. Pretreatment with the proteolytic enzyme pronase and the cross-linking agent paraformaldehyde abolished the capacity of lymphocytes to bind LPS. Inhibition by polymyxin B was less effective when added 30 min after initiation of incubation of LPS with cells at 0 C or when added at the initiation of incubation at 37 C. These results suggest that the interaction between LPS and lymphocytes is a two-stage process, the first of which is dependent on a positively charged membrane protein. The second stage is postulated to be an irreversible hydrophobic interaction between LPS and membrane lipids.

Animals↗
PubMedDate not supplied

Cervical paraganglioma with intranuclear vacuoles in a fine needle aspirate.

In a 56-year-old man who presented with a cervical mass, a fine needle aspiration specimen was suggestive of a papillary thyroid adenocarcinoma because of the presence of prominent intranuclear vacuoles in rare cells. Operation and subsequent examination of the mass removed from the bifurcation of the carotid artery clearly identified a paraganglioma. This case emphasizes the following points: aspirates of cervical paragangliomas are difficult to interpret, especially when scanty; intranuclear vacuoles are found in cells of a variety of cervical lesions, including paragangliomas, and should not in themselves define the diagnosis of papillary thyroid adenocarcinoma; and aspiration of cervical paragangliomas is probably contraindicated (but may be done unwittingly from time to time).

Biopsy, Needle↗