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Biomedical subjects

L Weiss

Publications and source records attributed to L Weiss.

At least 127 records · Page 7Linked to original sources
PubMed1996

Anti-hepatitis B virus activity of N-acetyl-L-cysteine (NAC): new aspects of a well-established drug.

N-acetyl-L-cysteine (NAC) is commonly administered as an antidote against acetaminophen intoxication and is the preferred agent in the treatment of pulmonary diseases. It is furthermore commonly considered that it restrains human immunodeficiency virus (HIV) replication by scavenging reactive oxygen intermediates (ROI) and thus suppressing activation of nuclear factor kappa B (NF kappa B). We show here that NAC is in addition able to inhibit hepatitis B virus (HBV) replication, but by a mechanism independent of the intracellular level of reactive oxygen intermediates. Treatment of HBV-producing cell lines with NAC resulted in an at least 50-fold reduction of viral DNA in the tissue culture supernatant within 48 h. This decrease of viral DNA and thus of virions in the tissue culture supernatant is caused by a disturbance of the virus assembly, rather than by a reduction of viral transcripts. Our data strongly suggest a potential use of this well-established, non-toxic drug for the treatment of HBV infection. Since NAC, in contrast to interferon, exerts its anti-HBV activity at a posttranscriptional level, a combination of NAC with the established interferon therapy could also be considered.

Acetylcysteine↗
PubMed1996

Multifocal stenosing ulcerations of the small intestine revealing vasculitis associated with C2 deficiency.

A patient with cryptogenic multifocal ulcerous stenosing enteritis characterized by repeated bouts of intestinal obstruction, ulcerative stenosis of the small bowel relapsing after surgical resection, and steroid sensitivity is described. Fourteen strictures of the jejunum were found at laparotomy. Despite resection, abdominal pain persisted. Steroid therapy was effective but led to dependence. In our patient, cryptogenic multifocal ulcerous stenosing enteritis was associated with fever, asthma, Raynaud's phenomenon, sicca syndrome, heterozygous type I C2 deficiency (28-base pair gene deletion), stenosis, and aneurysms in selective mesenteric angiography. It is hypothesized that cryptogenic multifocal ulcerous stenosing enteritis might be related to a particular form of polyarteritis nodosa with mainly intestinal expression or to a yet unclassified independent vasculitis.

Adult↗
PubMed1996

Plasma levels of lipoprotein (a) do not predict progression of human chronic renal failure.

Chronic renal failure is frequently accompanied by elevated plasma levels of lipoprotein (a) [Lp(a)]. Elevated Lp(a) levels have been proposed to contribute not only to increased risk of atherosclerotic and thrombotic complications but also to the progression of renal insufficiency. To investigate whether higher Lp(a) plasma concentrations are associated with an accelerated rate of progression of renal insufficiency, we have correlated baseline plasma concentrations of Lp(a) with the progressive decline of renal function in an observational study of human chronic renal disease. Forty-nine non-diabetic patients (40 men, nine women) were studied as part of an observational study of patients with moderately advanced renal insufficiency. The average follow-up time of the patient population was 3.1 years, and the mean rate of decline in glomerular filtration rate (51Cr-EDTA clearance) was -2.8 (SD 4.1) ml/min/1.73 m2. The mean plasma concentration of Lp(a) at the beginning of the study was 19.2 (SD 18.6) mg/100 ml with a median value of 12.2 mg/100 ml. There was no association between the initial plasma concentration of Lp(a) and the rate of progression as assessed by linear regression analysis. Furthermore, the progression rate in patients within the highest quartile of the Lp(a) distribution (> or = 30 mg/100 ml) did not differ from that in patients with lower levels of Lp(a). In contrast, increased levels of apolipoprotein (apo) B, low-density lipoprotein (LDL)-cholesterol, and proteinuria were all significantly associated with a more rapid decline in renal function. Based on these results, it was concluded that elevated plasma levels of Lp(a) are not associated with an increased rate of progression of renal insufficiency in human chronic renal disease. However, the results of this study suggest that other apoB-containing lipoproteins may play a significant role in this process.

Adult↗
PubMed1996

Head rotation during internal jugular vein cannulation and the risk of carotid artery puncture.

We undertook a prospective laboratory study to examine the effect of head position on the relative positions of the carotid artery and the internal jugular vein (IJV). Volunteers (n = 12) from departmental staff, 18-60 yr of age, who had never undergone cannulation of the IJV underwent imaging of their IJV and carotid artery. With the subject in a 15 degrees Trendelenburg position, two-dimensional ultrasound images of the IJV and the carotid artery were obtained on the left and right sides of the neck at 2 and 4 cm from the clavicle along the lateral border of the sternal head of the sternocleidomastoid muscle at 0 degrees, 40 degrees, and 80 degrees of head rotation from the midline. The percent overlap of the carotid artery and IJV increased significantly at 40 degrees and 80 degrees head rotation to both the right and left (P < 0.05). Data from 2 and 4 cm above the clavicle did not differ and were pooled. The percent overlap was larger on the left than the right only with 80 degrees of head rotation (P < 0.05). The increased overlap of carotid artery and IJV with head rotation > 40 degrees increases the risk of inadvertent puncture of the carotid artery associated with the common occurrence of transfixion of the IJV before it is identified during needle withdrawal. The IJV frequently collapses with needle insertion. This may result in puncture of the posterior wall of the vessel, and thus of the carotid artery when the two vessels overlap. To decrease this risk, the head should be kept in as neutral a position as possible, that is < 40 degrees rotation, during IJV cannulation.

Adolescent↗
PubMed1996

Xp pseudoautosomal gene haploinsufficiency and linear growth deficiency in three girls with chromosome Xp22;Yq11 translocation.

Colony stimulating factor-2 receptor alpha (CSF2RA) and interleukin-3 receptor alpha (IL3RA), two genes from the chromosome Xp and Yp pseudoautosomal region (PAR), have been suggested as candidate genes for short stature in Turner syndrome. We report three girls with X;Y translocation (46,X,der(X)t(X;Y)(p22;q11) initially detected by amniocentesis. The terminal portion of the X chromosome distal to the translocation breakpoint at Xp22 was deleted on the derivative X chromosome in all three patients. Each had normal stature at birth, with greater than expected deceleration of growth velocity by the second year. Using fluorescence in situ hybridisation (FISH), we have shown deletion of the CSF2RA and IL3RA loci on the derivative X chromosomes of all three patients. The role of CSF2RA and IL3RA haploinsufficiency in linear growth and final adult stature is discussed. Additional studies, particularly of molecular deletions within the PAR, are needed to improve our understanding of the role of these and other PAR loci in the genetic control of adult stature.

Adolescent↗
PubMed1996

Autoantibodies to the collagen-like region of C1q are strongly associated with classical pathway-mediated hypocomplementemia in systemic lupus erythematosus.

We have investigated the presence of autoantibodies to the collagen-like region (CLR) of C1q and its relationship with classical pathway-dependent hypocomplementemia in patients with SLE. Antibodies to CLR/C1q were quantitated in the plasma of 113 unselected patients with SLE by ELISA, using purified CLR as antigen. Plasma concentration of C3, CH50 activity and C2 hemolytic activity were determined according to standard procedures. The prevalence of IgG antibodies to CLR/C1q in the study population was 33.6%. Plasma titers of anti-CLR/C1q autoantibodies showed a strong negative correlation with CH50 activity (p < 0.0001) and with plasma levels of C3 (p < 0.0001). Eighty-five percent of patients with severe complement consumption exhibited high titers of anti-CLR/C1q antibodies in plasma, independently of clinical disease activity. Anti-CLR/C1q antibodies were present in the plasma of 38% of patients with moderate classical pathway consumption and 14% of patients with no evidence of complement consumption. Analysis of sequential samples from six patients over a period of 18 to 24 months demonstrated that changes in CH50 activity mirrored those of the plasma titers of anti-CLR/C1q antibodies. Acquired hypocomplementemia through the classical pathway is strongly associated with the presence of anti-CLR/C1q autoantibodies in SLE. The results suggest that anti-CLR/C1q antibodies may perpetuate classical pathway activation, independently of clinical disease activity.

Autoantibodies↗
PubMed1996

The spleen in murine Plasmodium chabaudi adami malaria: stromal cells, T lymphocytes, and hematopoiesis.

Morphologic and functional changes in the spleen of BALB/cByJ mice in the course of Plasmodium chabaudi adami malaria were assessed by light and electron microscopy, augmented by probes of polystyrene spheres and autoradiography of injected 3H-uridine-labeled T lymphocytes. The initial phase of the disease (precrisis) was characterized by increasing parasitemia accompanied by a marked increase in spleen size and by anemia. Erythropoiesis predominated, but there was also plasmacytopoiesis and monocyte-macrophage differentiation. The white pulp increased due to enlargement of lymphatic nodules, and in the periarterial lymphatic sheath, plasma cells invade the area around the central artery. A decrease in splenic uptake was demonstrated by light microscopic analysis of concentration and distribution of intravenously injected, spleen-cleared polystyrene spheres. Stromal cells showing signs of intense protein secretion and increased branching were present. Branches of these cells, barrier cells, appeared to seal off from the blood the locules of filtration beds, protecting splenic erythropoiesis from parasitization. Barrier cells are recently recognized fibroblastic contractile stromal cells that fuse to form complex branched variform barriers used for such diverse functions as controlling blood flow and blood cell delivery into the circulation, sealing off the hematopoietic/immunologic colonies and regulating their proliferation and differentration through paracrine secretion. Normally present in marrow and spleen in limited numbers, barrier cells are quickly mobilized in hematopoietic/ immunologic stess. They may well be part of a larger system that includes the myofibroblasts of wound healing and myoepithelial cells. The following phase, crisis, was characterized by a sharp decrease in parasitemia, increased splenic uptake, and amelioration of the anemia. Again, the filtration beds were opened to the blood. In the succeeding phase of postcrisis, the structure of the spleen approached normalcy. Analysis of autoradiographs showed T cells from normal or immunized mice distributing equally to red pulp and white pulp at 1 hr after injection of isolated radioactively labeled T cells, but they increased in white pulp over time. A higher percentage of immune cells was found in the white pulp of mice on day 16 of infection, suggesting a role for these cells in the development of crisis. Interleukin-I-treated mice developed higher levels of parasitemia and lower levels of splenic uptake.

Animals↗
PubMed1996

Effect of deoxyspergualin on graft-versus-host disease and graft- versus-leukemia in mice.

The effect of 15-deoxyspergualin (DSG) on bone marrow (BM) engraftment and graft-versus-host disease (GVHD) was studied in mice across both major (MHC) and minor (MiHC) histocompatibility barriers. (BALB/c x C57BL/6)F1 mice were inoculated with C57BL/6 cells, CBA mice were given B10.BR cells and BALB/c mice were transplanted with B10.D2 cells. All recipient mice were irradiated lethally or sublethally prior to transplantation. DSG had no effect on engraftment of parental cells in F1 mice at both 2.5 mg/kg and 10 mg/kg given daily for 10 days after treatment. Survival of F1 recipients of C57BL/6 cells increased significantly with 2.5 mg/kg DSG (p < 0.05). Across MiHC, 75% of DSG-treated CBA mice survived transplant for more than 150 days. No effect on GVHD was observed in the B10.D2 --> BALB/c setting. DSG abolished graft-versus-leukemia (GVL) effects in F1 mice transplanted with both BM and spleen cells (20%) of C57BL/6 mice and additionally inoculated with B cell leukemia (BCL1). In summary, in the semi-allogeneic murine models presented here DSG prevented GVHD but at the same time suppressed GVL effects induced by the allograft. For clinical use, DSG might therefore be very useful for prevention of GVHD post-allogeneic bone marrow transplantation for non-malignant diseases or for leukemia.

Animals↗
PubMed1996

Stimulation of immune reconstitution by interleukin-7 after syngeneic bone marrow transplantation in mice.

Successful outcome of autologous bone marrow transplantation (BMT) is severely handicapped by susceptibility to infection and by a high rate of relapse. While quantitative aspects of the immune system generally return to normal within the first 3-4 months after BMT, the recovery of qualitative immune functions is prolonged. Since interleukin-7 (IL-7) has growth-promoting and differentiating effects on pre-B cells and immature thymocytes, its role in the recovery of immune functions was investigated in BALB/c mice after syngeneic BMT (sBMT). After sBMT, mice treated with human recombinant IL-7 (rIL-7) showed an 11.9-fold increase in thymic cellularity associated with an enhanced response to a mitogenic stimulus compared with the controls. rIL-7 significantly increased RAG-1 expression and promoted V beta 8(D)J gene rearrangement of the T cell receptor in the thymus. Further, the cytokine boosted survival after challenge with influenza virus following sBMT. The finding that rIL-7 induces differentiation and proliferation of immature thymocytes and counteracts post-BMT immune deficiency makes it a promising medium for clinical application in BMT patients.

Animals↗
PubMed1996

Enhancement of primary and secondary responses to sheep red blood cells and influenza virus in BALB/c mice by recombinant human interleukin-2.

Treatment with recombinant human IL-2 (rIL-2) is being investigated as a new modality for the control of minimal residual disease in conjunction with autologous bone marrow transplantation for a variety of malignant hematological disorders and certain solid tumors. In investigating the functional role of rIL-2 in T cell dependent humoral immune responses, we determined the level of IgG, IgM, and total antibodies activity in BALB/c mice, with or without rIL-2 administration, before primary or secondary immunization with sheep red blood cells (SRBC) or influenza virus A/PR8/34 (H1N1). Our results show the beneficial effect of pretreatment with rIL-2 in enhancing primary and secondary humoral immune responses to SRBC (p < 0.05) and possibly to influenza virus. Administration of well tolerated doses of rIL-2 before inoculation of antigen or infectious agent is not likely to be harmful and may even enhance protective immunological responses.

Animals↗
PubMed1996

Soluble tumor necrosis factor (sTNF) receptors: a possible prognostic marker for bone marrow transplantation-related complications.

Involvement of tumor necrosis factor (TNF) in bone marrow transplantation (BMT)-associated complications has been documented. Biological response to TNF requires interaction with specific cell membrane receptors. Extracellular domains of these receptors are released into body fluids as soluble molecules, and participate in the bioactivity of TNF. Serum levels of p55 and p75 soluble tumor necrosis factor receptors (sTNFR) were determined in 34 patients with different diseases who underwent BMT. Sequential studies initiated 10 days before BMT and continued up to 110 days post-transplantation showed that p55 and p75 sTNFR levels were elevated significantly in patients who subsequently developed major transplant-related complications (TRC). Moreover, both sTNFR levels were increased 2- to 3-fold over control values during post-BMT febrile periods in those patients who at a later stage suffered major TRC. These results indicate that the serum level of sTNFR may be used as a prognostic marker for major TRC in BMT.

Adolescent↗
PubMed1995

Triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) induces nuclear translocation of NF-kappa B (p50/p65) in human monocytes and enhances viral replication in HIV-infected monocytic cells.

Monocyte/macrophages may harbor HIV in a nonproductive fashion for prolonged periods of time. Viral gene expression may be reactivated by stimulation of the cells with LPS or cytokines such as TNF-alpha in vitro. The effect of LPS and TNF-alpha is mediated by their ability to induce nuclear translocation of the DNA-binding heterodimer NF-kappa B (p50/p65), which binds to a specific sequence in the HIV-long terminal repeat. The present study demonstrates that triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) enhances viral replication in HIV-infected human monocytic cells. Monocytic cell lines and normal peripheral blood monocytes were infected with HIV-1 in vitro and cultured in the presence or absence of F(ab')2 fragments of monoclonal anti-CR1 or anti-CR3 Abs or with C3 fragments. Stimulation of CR1 or CR3 induces a two- to fourfold increase in the amount of cell-associated and released p24 Ag in cell cultures that was equivalent to that observed in control cultures triggered with LPS. We further observed that stimulation of CR1 or CR3 induces the nuclear translocation of NF-kappa B p50/p65 in infected cells. Translocation of NF-kappa B p50/p65 was also observed following stimulation of CR1 or CR3 of uninfected peripheral blood monocytes from HIV-seronegative donors. The amount of protein translocated was similar to that observed when cells were stimulated with rhTNF-alpha. TNF-alpha did not mediate the translocation of NF-kappa B p50/p65 induced by triggering of complement receptors. Taken together, these observations suggest that HIV gene expression may be activated in infected monocytes through interaction of the cells with complement-opsonized particles and that enhanced viral replication is associated with C3 receptor-mediated nuclear translocation of the NF-kappa B complex.

Biological Transport↗
PubMed1995

[Partial properdin deficiency revealed by a septicemia caused by Neisseria meningitidis].

Properdin is one of the regulatory proteins of the alternative pathway of the complement system. Human properdin deficiency is an X-linked disorder strongly predisposing to meningococcal disease. Total deficiency (type I), partial deficiency (type II), and deficiency due to a dysfunctional molecule (type III) can be differentiated immunochemically. Four males in a family showed a selective partial deficiency of properdin. These individuals had 10% of normal properdin concentration in plasma, as measured by ELISA, while the other complement components were normal. Two of the properdin-deficient individuals in two generations had meningococcal infections. Two were clinically healthy at the time of investigation. Measurement of plasma levels of properdin has to be performed in the case of Neisseria meningitidis, especially where there is a previous history of severe bacterial infections in the same family as measurement of CH50 activity is ineffective for screening properdin deficiency.

Bacteremia↗
PubMed1995

CD14lowCD16high: a cytokine-producing monocyte subset which expands during human immunodeficiency virus infection.

Infection with the human immunodeficiency virus HIV-1 is associated with the expansion of a CD14lowCD16high monocyte subset in peripheral blood. This subset, which represents a minor subpopulation of monocytes in healthy individuals, increases during HIV infection and, in patients with AIDS, may represent up to 40% of the total circulating monocyte cell population. The CD14lowCD16high circulating monocytes co-express MAX.1, p150,95 and HLA-DR which are typical of tissue macrophage markers. These cells also express higher levels of intracellular interleukin (IL)-1 alpha and tumor necrosis factor (TNF)-alpha than the CD14highCD16low monocyte population from the same patients. The CD14lowCD16high cells also express low levels of CD35, CD11a and CD4 in common with normal monocytes. When cultured in vitro, monocytes from HIV-seropositive individuals differentiated within a few hours into an elongated fibroblastoid shape characteristic of migratory cells. Our results suggest that the expansion of the CD14lowCD16high monocyte subset, which produce high amount sof TNF-alpha and IL-1 alpha, may participate in the immune dysfunction observed during HIV infection.

Cell Division↗
PubMed1995

Anti-cardiolipin antibodies are associated with anti-endothelial cell antibodies but not with anti-beta 2 glycoprotein I antibodies in HIV infection.

HIV infection is associated with polyclonal increase in serum immunoglobulins and with elevated titers of serum antibodies to a variety of self antigens, including anti-phospholipid antibodies. In the present study, we found a high prevalence of 46.8% of serum IgG anticardiolipin antibodies (ACA) in a group of 111 unselected HIV-seropositive individuals. The presence of ACA was correlated with that of IgG antibodies to endothelial cells (AECA) but not with that of anti-beta 2 glycoprotein I antibodies, that were only found in 7.4% of the patients. The presence of IgG ACA was not associated with detectable lupus anticoagulant activity, nor with a history of thrombosis. Serum titers of ACA were not correlated with absolute numbers of circulating CD4+ cells. We found no relationship between the presence and titers of ACA, hypergammaglobulinemia, and serum titers of natural IgG autoantibodies to a panel of self antigens. Our results suggest that increased titers of ACA in HIV infection result from a biased expansion of B cell clones producing natural autoantibodies.

Adult↗