Search PubMed⌕ Search

Biomedical subjects

L Weiss

Publications and source records attributed to L Weiss.

At least 235 records · Page 13Linked to original sources
PubMed1991

Myocardial beta-adrenergic adenylate cyclase complex in a canine model of chagasic cardiomyopathy.

Infection of beagles with an opossum-derived strain of Trypanosoma cruzi (Tc-O) results in features of early and chronic chagasic cardiomyopathy, that is, increases in PR interval, atrioventricular block, and frequent ventricular premature contractions, ventricular tachycardia, and decreased left ventricular ejection fraction. These signs are not observed in animals infected with a canine strain of T. cruzi (Tc-D). To understand the biochemical basis for these early cardiac effects, we examined the beta-adrenergic adenylate cyclase complex in myocardial membranes prepared from animals infected with either of the two strains. In animals infected with Tc-O (symptomatic), the maximum velocity (Vmax) decreased and concentration of agonist resulting in 50% of Vmax (Kact) increased for isoproterenol-dependent adenylate cyclase activity; in animals infected with Tc-D (asymptomatic), Vmax and Kact for isoproterenol were unchanged from control, uninfected animals. beta-Receptor density decreased by 20% in symptomatic animals with no change in affinity, whereas no differences were observed between uninfected and infected asymptomatic animals. A complex pattern of changes was apparent in the guanine nucleotide binding protein, Gs, in the setting of infection. Alterations in cholera toxin-dependent ADP-ribosylation patterns as well as immunochemical detection with anti-G alpha s antisera suggested a change in the biochemical nature of the Gs species and not necessarily a physical loss of this protein. Reconstitution of adenylate cyclase activity in cyc- membranes demonstrated a decrease in hormone-sensitive Gs activity in membranes prepared from symptomatic animals without a change in activity demonstrable in the presence of Gpp(NH)p. Collectively, the results suggest that the depression in beta-adrenergic adenylate cyclase activity associated with symptomatic infection of beagles with T. cruzi occurs primarily as a result of changes in the Gs protein complex, most likely resulting in an uncoupling of the beta-adrenergic receptor from the Gs protein.

Adenosine Diphosphate Ribose↗
PubMed1991

Recombinant human superoxide dismutases: production and potential therapeutical uses.

In many pathological situations, tissue damage is caused by cellular generation of superoxide free radicals (O2-). These active species are generated during post-ischemic reperfusion of organs, in hyperoxic tissue, during acute and chronic inflammation and during exposure to ionizing radiation. Exogenous superoxide dismutase (SOD) was shown to significantly prevent such damage. The genes for human cytosolic Cu/ZnSOD and mitochondrial MnSOD were cloned and introduced into an E. coli expression system. The proteins were expressed in high yields and purified to homogeneity, yielding pharmaceutical-grade materials. These enzymes were used in a variety of in vivo animal models for the demonstration of their protective effects against oxidative damage. Comparative pharmacokinetic studies in rats have revealed that the half-life of Cu/ZnSOD was 6-10 min., while that of MnSOD was 5-6 hours, thus indicating that MnSOD may be superior to Cu/ZnSOD for the treatment of chronic diseases. Indeed, MnSOD was found to be effective as an anti-inflammatory agent in the rat carrageenan induced paw edema acute inflammation model. Both enzymes were also effective in ameliorating post-irradiation damage in mice exposed to whole-body or localized chest X-ray radiation.

Animals↗
PubMed1991

Measurements of compression of Ehrlich ascites tumor cells and their relevance to hematogenous metastasis.

Ehrlich ascites cancer cells were compressed between glass microscope slides by the addition of weights. The projected areas of the cells were measured, and their surface membrane integrity determined by means of trypan-blue exclusion tests under different compression loads of 0 to 800g. The results are compatible with a two-step mechanism for surface rupture; first the cell membrane is unfolded and then stretched, with modest degrees of stretching associated with membrane rupture. It is calculated that lethal surface membrane rupture of the type produced here by compression, could also be produced when cancer cells are deformed by entry and passage along relatively non-deformable capillaries. This would at least partially account for the rapid destruction of cancer cells in the microcirculation. The observation that isolated nuclei are less deformable than whole cells, may indicate that their nuclei may protect cancer cells from biomechanical trauma.

Animals↗
PubMed1991

The effect of total or partial T lymphocyte depletion on susceptibility to influenza virus infection and development of antiviral immunity in lethally irradiated mice reconstituted with immune syngeneic bone marrow grafts.

In a previous study, we showed that lethally irradiated mice reconstituted with bone marrow (BM) enriched with spleen cells obtained from A/PR8/34 influenza virus-immune donors had an improved survival rate compared to the survival seen in recipients of naive BM, immune BM or T cell-depleted BM obtained from immune mice. Our purpose was to determine which cell population was responsible for this effect. We therefore compared the resistance to influenza virus of lethally irradiated BALB/c mice reconstituted with BM from immune donors enriched with 20% spleen cells following either incubation with anti-Thy-1, anti-Lyt-2 or anti-L3T4 monoclonal antibodies prior to transplantation, thereby leading to in vivo depletion of antibody-treated lymphocyte subsets. Mice were infected with influenza virus 1 day after BM transplantation. Equal survival rates were observed in recipients of unmanipulated BM and spleen cells obtained from immune donors and recipients of similar inocula treated with monoclonal anti-helper (L3T4) or anti-cytotoxic/suppressor (Lyt-2) antibodies prior to inoculation. The survival rate of all these groups was increased in comparison with mice receiving anti-Thy-1 treated BM and spleen cells, suggesting that both L3T4 and Lyt-2 T cell subsets play a role in protection against virus infections.

Animals↗
PubMed1991

Effects of cytoskeletal perturbation on the sensitivity of Ehrlich ascites tumor cell surface membranes to mechanical trauma.

Evidence presented previously indicated that shape changes in circulating cancer cells within the microvasculature may lead to rapid, lethal rupture of the cell surface membranes, thereby contributing to the inefficiency of this phase of hematogenous metastasis. As the cytoskeleton is known to regulate cell shape and, in at least some cases, to be attached to the surface membrane, we have determined whether or not it plays a role in inhibiting lethal, deformation-associated, mechanically induced surface membrane trauma. Thus, Ehrlich ascites tumor (EAT) cells were treated with different cytoskeleton-perturbing agents, and their susceptibility to filtration trauma on passage through Nuclepore membranes was determined. In contrast to the involvement of the cytoskeleton in nonlethal cell deformation, agents which disrupt intracellular networks of microtubules, microfilaments and intermediate filaments had little or no direct effect on EAT cell susceptibility to rapid, mechanically induced, lethal trauma.

Acrylamide↗
PubMed1991

[Structure and function of receptors for C3 cleavage fragments].

Most of the biological effects derived from complement activation depends on interactions between cleavage fragments of complement components and cells bearing specific receptors. This review overviews structure and function of receptors for C3 cleavage fragments. Genes encoding for CR1, CR2 and CR3 have been cloned and they code for integral transmembrane glycoproteins which function as cellular receptors for human C3b, C3dg/C3d and C3bi fragments respectively. These receptors have a wide cellular distribution and participate in transport of immune complexes, phagocytosis and regulation of immune response. Alterations of expression of these molecules are observed in pathology.

Complement C3↗
PubMed1991

Resolution of Cryptosporidium infection in an AIDS patient after improvement of nutritional and immune status with octreotide.

An AIDS patient with severe large volume diarrhea and malnutrition due to cryptosporidial infection is presented. The patient, who was not receiving zidovudine, was treated with octreotide with resolution of diarrhea leading to improvement in nutritional status, immune functions, and subsequently, resolution of the Cryptosporidium infection. This case points out the need for adequate nutrition in AIDS patients and highlights the relationship of nutrition and the immune system.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Quantitation of endogenous lectin expression in 3LL tumors, growing subcutaneously and in the kidneys of mice.

By means of microdensitometry and image analysis, quantitative measurements were compared of endogenous lectin expression in tissue sections from 3LL carcinomas growing in the subcutis and kidneys of mice following the direct injection of cancer cells. The lectins were visualized by means of a modification of the ABC-peroxidase technique. In comparison with the subjective, visual inspection of similar materials reported previously, these quantitative techniques not only confirmed, but also provided additional information on site-associated changes in 3LL cell populations. Previously, 2 classes of cancer cells were recognized within the tumors on the basis of staining intensity, compared with 3 classes in the present study and, in addition, the relative areas occupied by these 3 densitometric classes were determined by image-analysis. Both "low" and "high" integrated intensities were significantly greater in the kidney tumors in 11 of 24 cases, and in 6 of 24 cases of s.c. tumors. The areas occupied by "high" and "low" intensity cells were significantly higher in 14 of 24 kidney tumors, and in 2 of 24 s.c. tumors. The results indicate often marked differences in endogenous lectin expression, between 3LL cancer cells from a common source, after direct delivery and growth in 2 different anatomic sites. These results indicate the necessity of taking into account analogous changes, when comparing these and other properties of cancer cell populations in metastases with those in primary tumors, with respect to both the generation of site-associated differences and their possible site-associated abrogation.

Animals↗
PubMed1990

[Lupus and protein deficiencies of the classical complement pathway].

Deficiencies in proteins of the classic complement pathway are particularly frequent in patients with autoimmune diseases, notably systemic lupus erythematosus (SLE). The C4 component is a polymorphous glucoprotein coded by two closely linked genes, C4A and C4B, located within the HLA complex. C4, and in particular the C4A isotype plays a major role in maintaining immune complexes in solution. Fifty percent of patients with SLE are homozygous or heterozygous to the silent allele C4 AQO. Hereditary CE deficiency is often complicated by lupus-related diseases which may be associated with repeated infections. The biological particularity of SLE associated with complement protein deficiencies is the frequency of anti-SSA (Ro) antibodies.

Complement C2↗
PubMed1990

Contributions of vascularized lymph-node metastases to hematogenous metastasis in a rat mammary carcinoma.

Rats received hind-foot-web (FWI) injections of MT-100-TC mammary carcinoma cells; the resultant tumor metastasized first to the popliteal lymph nodes. Over the course of 4 weeks, in association with increases in tumor weight, the blood-flow to the popliteal nodes increased 18-fold, and their vascular densities increased 2-fold. In spite of this vascularization, cancer cells were detected in only 3 of 648 blood vessels associated with involved, ipsilateral lymph nodes compared with intravascular cells in 82 of 314 vessels associated with "primary" foot-pad lesions. The presence of tumorigenic cancer cells in the right ventricular blood of animals bearing these tumors is, therefore, considered to result from their direct entry into blood vessels from the "primary" lesions, and/or from extra-nodal invasion of vessels in tissues to which nodal tumors were adherent, as distinct from passage via lymphatico-venous communications between tumors and nodal blood-vessels. The reconstructed events occurring in the rat model, with effective restriction of regional node metastases to the nodes themselves for a time, could possibly account for the long-term survival of some patients with breast cancer and regional-node metastases, following surgery.

Animals↗
PubMed1990

[Chronic urticaria and acquired complement deficiency due to a nephritic factor (C3NeF)].

Several studies have suggested that complement activation processes are frequently involved in the pathogenesis of urticaria. We report clinical evolution and studies of complement-mediated functions in a 47-year-old previously described patient presenting with chronic urticaria, in whom we found persistent low complement hemolytic activity (65-75% of normal values), depressed levels of third complement component (C3, between 55% and 65%) and of factor B (between 60% and 75%), together with C1, C4, C2, C5, C5b neoantigen and fluid phase terminal complement (SC5b-9) complex within the normal range, pointing to activation of the alternative pathway. A circulating low affinity C3 nephritic factor (C3NeF), known to enhance cleavage of human serum C3, was detected. The urticarial lesions, which were initially pruritic and persisted for less than 24 hours, became subsequently fixed and burning, and were accompanied by fever and arthralgia. Skin biopsy specimens showed moderate leukocytoclastic vasculitis. Response to varied treatment regimens, including antihistamines and colchicine, was poor. Therapy with oral corticosteroids produced some improvement. The association of chronic urticaria with C3NeF without clinical and biological signs of membranoproliferative glomerulonephritis and partial lipodystrophy has not to our knowledge been reported before. This observation raises the question of a possible role of C3NeF in the pathogenesis of urticaria.

Chronic Disease↗
PubMed1990

Cytogenetic study of four cancers of the prostate.

We cytogenetically studied four cases of adenocarcinoma of the prostate. All tumors were moderately differentiated or well-differentiated, with different degrees of invasion. One tumor with microscopic seminal vesicle invasion and lymph node metastasis (tumor 4) had trisomy 7 as a sole clonal abnormality, suggesting that this is a primary change in some prostatic tumors. Although only normal karyotypes were observed in the other three tumors, several nonclonal changes were evident. Monosomy 9 or deletion of the long arm of 9 was observed in at least one cell in the three tumors without trisomy 7. Furthermore, in one of these tumors (tumor 3, moderately differentiated), several rearrangements (five of 26 cells) were observed, two of which had a common breakpoint at 15q11. Although complex chromosome changes including del(10q) and del(7q) have been described in prostatic tumors, they were not observed in the four tumors studied. This is the first report of a prostate tumor with trisomy 7 as a single clonal chromosome abnormality.

Adenocarcinoma↗
PubMed1990

Deep splenic lymphatic vessels in the mouse: a route of splenic exit for recirculating lymphocytes.

A study of pathways of lymphocyte migration through mouse spleen revealed lymphatic channels closely following arteries in trabeculae and white pulp. Because there is no detailed record of the layout of deep splenic lymphatics in the mouse, or other species, we present our observations in this paper, relating our findings to normal migratory pathways of lymphocytes through the spleen. Lymphatics draining the spleen are so inconspicuous that they often are not mentioned in anatomical discussions. The data presented clearly demonstrate 1) the existence and layout of deep lymphatic vessels in the mouse spleen, and 2) that migrating lymphocytes exit white pulp via these lymphatic vessels. CD4+ and CD8+ T cell subsets migrated proximally along the central artery from distal (dPALS) to proximal periarterial lymphatic sheaths (pPALS) and exited via deep lymphatic vessels that originate there. B cells migrated from dPALS to enter lymphatic nodules (NOD), thus segregated from T cells. B cells then migrated toward and exited via deep lymphatics. The appearance of labelled lymphocytes in lymph coincided with their disappearance from white pulp compartments. Labelled T cells were observed in splenic lymphatics as early as 1 hr after intravenous infusion but took, on average, about 6 hr. B cells took somewhat longer. Thus T and B cells entered and left white pulp through shared pathways, but took divergent intermediate routes through dedicated zones, pPALS for T cells, NOD for B cells.

Animals↗
PubMed1990

Migration pathways of recirculating murine B cells and CD4+ and CD8+ T lymphocytes.

Migration pathways of B cell and CD4+ and CD8+ T cell subsets of murine thoracic duct lymphocytes (TDL) were mapped. Per weight, the spleen accumulated more TDL than any other organ, regardless of lymphocyte subset. Spleen autoradiographs showed early accumulations of TDL in marginal zone and red pulp. Many TDL exited the red pulp within 1 hr via splenic veins. The remaining TDL entered the white pulp, not directly from the adjacent marginal zone but via distal periarterial lymphatic sheaths (dPALS). From dPALS, T cells migrated proximally along the central artery into proximal sheaths (pPALS) and exited the white pulp via deep lymphatic vessels. B cells left dPALS to enter lymphatic nodules (NOD), then also exited via deep lymphatics. T cells homed to lymph nodes more efficiently than B cells. Lymphocytes entered nodes via high-endothelial venules (HEV). CD4+ TDL reached higher absolute concentrations in diffuse cortex than did CD8+ T cells. However, CD8+ TDL moved more quickly through diffuse cortex than did CD4+ TDL. B cells migrated from HEV into NOD. Both T and B TDL exited via cortical and medullary sinuses and efferent lymphatics. A migration pathway across medullary cords is described. All TDL subsets homed equally well to Peyer's patches. T TDL migrated from HEV into paranodular zones while B cells moved from HEV into NOD. All TDL exited via lymphatics. Few TDL entered zones beneath dome epithelium. All subsets were observed within indentations in presumptive M cells of the dome epithelium.

Animals↗
PubMed1990

Induction of cell-associated interleukin 1 through stimulation of the adhesion-promoting proteins LFA-1 (CD11a/CD18) and CR3 (CD11b/CD18) of human monocytes.

Serum-free culture of human monocytes in the presence of monoclonal antibodies to the LFA-1 alpha chain (CD11a), CR3 alpha chain (CD11b) or beta chain (CD18) bound to Sepharose induced the dose-dependent production of cell-associated interleukin (IL) 1 activity and of IL 1 alpha and IL 1 beta antigens, but no release of extracellular IL 1 activity or antigen in the culture medium. Triggering of IL 1 production was also observed with insolubilized anti-CD11/CD18 F(ab')2 antibodies. Two cross-linked antibodies recognizing distinct epitopes on the CD11b molecule induced cell-associated IL 1. Soluble antibodies did not induce IL 1 production. The kinetics of induction of IL 1 by stimulation of adhesion-promoting proteins differed from those of IL 1 induction by adhesion to plastic. The lack of induction of IL 1 release by stimulation of the CD11/CD18 molecules resembled the intracellular accumulation of IL 1 induced by lipid A. Induction of IL 1 by adhesive processes may be a mechanism by which T cells trigger IL 1 production by monocytes during antigen presentation.

Antigens, Differentiation↗