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Biomedical subjects

M Goldman

Publications and source records attributed to M Goldman.

At least 163 records · Page 9Linked to original sources
PubMed1998

Stroke recurrence is more frequent in Blacks and Hispanics.

This study was designed to measure recurrent stroke rates and identify their determinants in a mixed ethnic population. A cohort of 299 patients (110 black, 57 Hispanic and 132 white) admitted to a large urban hospital with an acute stroke between November 1, 1991, and July 1, 1993, was followed for a mean of 17.8 months. Demographic and historical data and stroke subtype and severity were recorded at the time of the index stroke. The main outcome measure was stroke recurrence. The unadjusted relative risk of stroke recurrence for blacks, relative to white, was 2.0 (95% CI: 0.9-4.4) and for Hispanics, relative to whites, it was 2.6 (95% CI: 1.08-60). Ethnicity appeared to be associated with recurrence risk only among first-ever strokes: the risk for blacks, relative to whites, was 2.4 (95% CI: 1.02-5.5) and for Hispanics it was 2.9 (95% CI: 1.2-7.4). None of the other putative risk factors for stroke recurrence identified at the time of initial hospitalization were associated with risk of recurrence.

Black or African American↗
PubMed1998

A new noninvasive technique for imaging atherosclerotic plaque in the aortic arch of stroke patients by transcutaneous real-time B-mode ultrasonography: an initial report.

BACKGROUND AND PURPOSE: Aortic arch atherosclerotic plaque is a probable source of atheroembolic stroke. Transesophageal echocardiography (TEE) has been used to image the aorta of patients with stroke to identify atherosclerotic plaque. TEE is moderately invasive and does not always visualize plaques present in the distal ascending aorta and proximal aortic arch. METHODS: In the current study, transcutaneous B-mode ultrasonography was performed to image the aortic arch through a lateral supraclavicular window, and the results were compared with those of TEE in 20 patients. The aorta was subdivided into the proximal ascending (PAsc), distal ascending (DAsc), proximal aortic arch (PAA), and distal aortic arch (DAA) to be certain the plaques identified by each technique were the same. Plaques were characterized as simple (<4 mm thick) or complex (>4 mm thick). RESULTS: In the PAsc, 8 simple plaques were identified with TEE but not with B-mode. In the DAsc, 1 complex plaque was identified with both techniques, and B-mode identified 1 additional complex and 1 simple plaque. In the PAA, 6 simple and 5 complex plaques were identified by both techniques, and TEE identified 1 additional complex plaque. In the DAA, TEE identified 2 simple and 2 complex plaques; B-mode identified 3 complex plaques. CONCLUSIONS: B-mode imaging compared favorably with TEE in identification of plaques in the aortic arch and distal ascending aorta, although it could not identify simple plaques in the proximal ascending. B-mode could visualize plaques not seen by TEE in the distal ascending aorta. B-mode ultrasonography is complementary to TEE in performance of a comprehensive assessment of plaque in the aortic arch and provides a noninvasive method for sequential studies of plaques that can be visualized.

Aorta, Thoracic↗
PubMed1998

The idiopathic hypereosinophilic syndrome: clinical presentation, pathogenesis and therapeutic strategies.

The idiopathic hypereosinophilic syndrome (HES) is a heterogenous disease entity characterized by persistent unexplained hypereosinophilia generally complicated by end-organ damage. Correct diagnosis and management are important in order to prevent long-term complications. Furthermore, it appears that HES represents a premalignant state in some patients, and close follow-up is necessary to detect early signs of malignant transformation. Previous studies of patient cohorts have led to the identification of a subgroup of patients with various clinical and biological features of primitive myeloproliferative disease. Patients in this subgroup have a clinically more aggressive disease in terms of organ damage and eventually develop acute myeloid leukemia. Among the remaining patients, it appears that some present an underlying T-cell disorder characterized by overproduction of Th2-type cytokines in vivo. Indeed, lymphocytes belonging to the Th2 subset are implicated in the maturation, activation and recruitment of eosinophils, essentially through the production of IL-5. Such patients appear to present a more benign disease at short term; however, they may develop T-cell lymphoma years after initial diagnosis. Therapy of HES includes glucocorticoids, hydroxyurea and more recently, interferon-alpha. Prednisone is generally recommended initially, followed by hydroxyurea in case of treatment failure. Until now, interferon-alpha has been reserved for refractory cases of HES. Our proposal for a new treatment strategy, based on current understanding of the pathogenesis of different subgroups of HES and on the mechanisms of action of the proposed therapeutic agents, which will be discussed in detail. Moreover, prevention of malignant transformation has become a new subject of concern when considering the beneficial effects of drugs.

Journal Article↗
PubMed1998

Interleukin-10 as a regulatory cytokine induced by cellular stress: molecular aspects.

Interleukin-10 is an ubiquitous cytokine which plays a major regulatory role in the course of inflammatory responses by downregulating the synthesis of cytokines. In this paper, we summarize the major biological properties of IL-10 and the current knowledge of the molecular mechanisms by which IL-10 inhibits the expression of genes encoding proinflammatory cytokines. We then review the factors upregulating IL-10 synthesis and we present the concept that IL-10 is a stress cytokine produced not only in response to microbial pathogens but also to cellular injuries of diverse origins.

Animals↗
PubMed1998

Lipid formulations of amphotericin B.

Amphotericin B has long been the mainstay in the treatment of systemic fungal infections, but its nephrotoxicity limits the dosage that can be used. New lipid-based forms may allow higher dosing with less nephrotoxicity. Unfortunately, these new forms are substantially more expensive, and data from randomized clinical trials of their relative efficacy are as yet limited.

Amphotericin B↗
PubMed1998

CD40 engagement on endothelial cells promotes tissue factor-dependent procoagulant activity.

The CD40 molecule expressed on endothelial cells has been shown to transduce activation signals resulting in upregulation of adhesion molecules. Herein, we studied the impact of CD40 engagement on the induction of tissue factor (TF)-dependent procoagulant activity (PCA) at the surface of human umbilical vein endothelial cells (HUVECs). First, we found that co-incubation of HUVECs with 3T6 fibroblasts transfected with the CD40L gene (3T6-CD40L) resulted in a clear induction of PCA which was not observed with control untransfected fibroblasts. The specificity of this finding was established by inhibition experiments using monoclonal antibodies (mAbs) blocking CD40 or CD40L. PCA induced by CD40 ligation was TF-related as it was not observed in factor VII-deficient plasma and was associated with the accumulation of TF mRNA. To investigate the role of CD40/CD40L interactions in the induction of endothelial cell PCA by lymphocytes, interferon (IFN)-gamma-stimulated EC were incubated with T cells in the absence or presence of anti-CD40 or anti-CD40L mAb. The 60-70% inhibition of PCA induced by these mAbs but not their isotype-matched control indicated that the CD40 pathway is involved in the induction of PCA resulting from interactions between activated HUVECs and T cells. We conclude that activation signals elicited by CD40 engagement on endothelial cells result in the induction of TF-dependent PCA. The CD40/CD40L pathway might therefore be involved in the development of prothrombic states during diseases associated with endothelial cell and T cell activation.

Blood Coagulation↗
PubMed1998

Methotrexate inhibits LPS-induced tumor necrosis factor production in vivo.

We investigated the effects of methotrexate (MTX) on the production of tumor necrosis factor (TNF), nitric oxide (NO) and interleukin-10 (IL-10) in vivo. Administration of low doses of MTX (450 mug/kg once a week for 4 weeks) in Balb/c mice resulted in a significant inhibition of the systemic release of TNF and NO upon LPS challenge, whereas the production of IL-10 remained unchanged. These anti-inflammatory effects of MTX were exerted at the macrophage level since peritoneal macrophages from mice, injected for 4 weeks with MTX produced lower levels of TNF than cells from control mice upon LPS stimulation ex vivo. In parallel, we found that MTX-treated mice were less susceptible to a lethal challenge with LPS and D-galactosamine. MTX did not inhibit TNF release after injection of Concanavalin A (ConA) or anti-CD3 monoclonal antibody (mAb), indicating that MTX does not inhibit TNF production at the T cell level. We conclude that repeated administration of a low dose of MTX in mice is associated with a decreased production of TNF by macrophages upon LPS activation.

Animals↗
PubMed1997

Protective effect of a single interleukin-12 (IL-12) predose against the toxicity of subsequent chronic IL-12 in mice: role of cytokines and glucocorticoids.

The mechanisms of interleukin-12 (IL-12) toxicity were studied in mice using a schedule (murine rIL-12, 400 ng/mouse, intraperitoneally [IP] once daily for 5 days) that markedly reduced body weight and food intake. On day 5, IL-12-treated mice had elevated serum and spleen IFN-gamma and tumor necrosis factor (TNF). Serum sTNFR-P75 and corticosterone (CS) were also elevated. IL-12 toxicity was partially prevented by anti-IFN-gamma antibodies or dexamethasone (DEX). A pre-dose of IL-12 (200 ng/mouse on day -14) completely prevented the toxicity of subsequent IL-12. The IL-12 predose also inhibited IL-12-induced IFN-gamma levels, but did not modify IL-12-induced CS, TNF or sTNFR-P75. A protective effect was observed with a predose of lipopolysaccharide (LPS) or murine recombinant (r)IL-10. The protective effect of the IL-12 predose was reduced by coadministration of anti-IFN-gamma, but a predose of murine rIFN-gamma was not protective, suggesting that IFN-gamma is necessary but not sufficient for the protective effect of IL-12. The IL-12 predose specifically protected against IL-12 toxicity and did not modify LPS toxicity. These data indicate that IL-12 can induce tolerance to its own toxicity, probably through a downregulation of IL-12-induced IFN-gamma but independently of endogenous glucocorticoids. IFN-gamma, and possibly IL-10, might be important in this tolerance.

Animals↗
PubMed1997

A pilot trial of recombinant human interleukin-10 in kidney transplant recipients receiving OKT3 induction therapy.

BACKGROUND: We conducted a randomized, double-blind, placebo-controlled, rising single-dose study to investigate the effects of recombinant human (rh) interleukin (IL) 10 in renal transplant patients who received OKT3 as induction therapy. METHODS: Patients received 0.1 (n=6), 1 (n=6), or 10 microg/kg (n=3) rhIL-10 or placebo (n=6) intravenously 30 min before the first injection of 5 mg of OKT3. We monitored IL-10 serum levels, the effect of rhIL-10 on OKT3-induced cytokine production, clinical toxicity, and the incidence of immunization against OKT3. RESULTS: Serum IL-10 levels in the three experimental groups reached 0.8+/-0.2, 7.9+/-1.3, and 118.6+/-7.3 ng/ml (mean+/-SEM), respectively, 30 min after rhIL-10 injection. Peak plasma levels of tumor necrosis factor-alpha (TNF-alpha) were reduced from 2953+/-1599 pg/ml in patients injected with OKT3 and placebo to 447+/-155, 703+/-246, and 459+/-246 pg/ml in patients injected with 0.1, 1, and 10 microg/kg rhIL-10, respectively. Values for 24-hr TNF-alpha area under the curve decreased from 8988+/-3551 pg x hr/ml in control patients to 2284+/-494, 3950+/-955, and 2420+/-931 pg x hr/ml for the 0.1, 1, and 10 microg/kg rhIL-10 dose groups, respectively (P=0.045). There was also a trend toward reduced plasma levels of IL-2, IL-8, and interferon-gamma in rhIL-10-pretreated patients. Although none of the patients who received placebo or 0.1 or 1 microg/kg rhIL-10 developed an IgM antibody response directed against OKT3 during the first 10 days, this occurred in all three patients who received the highest rhIL-10 dose. In two of these patients, neutralization of OKT3 was associated with a reversible acute rejection episode. CONCLUSIONS: Pretreatment with doses of up to 1 microg/kg rhIL-10 is safe and reduces the release of TNF-alpha induced by OKT3. However, higher doses might promote early sensitization to OKT3.

Adult↗
PubMed1997

Lung rejection occurs in lung transplant recipients with blood chimerism.

BACKGROUND: It has been postulated that chimerism after transplantation might promote graft acceptance. In the present study, we prospectively assessed blood chimerism in 10 lung transplant recipients during the first posttransplant year and investigated whether chimerism was associated with an immunologically stable situation of the graft. METHODS: The recipients' peripheral blood mononuclear cells were obtained before transplantation and at various time points during the first postoperative year. Donor cells were detected using nested polymerase chain reaction amplification of a donor-specific HLA-DRB1 allele. Clinical graft acceptance was determined by the number of rejection episodes. RESULTS: The incidence of blood chimerism was high during the first 3 postoperative months and then decreased over time. All patients experienced at least one acute rejection episode, and three patients developed chronic rejection. CONCLUSION: We, thus, conclude that rejection of the lung allograft may occur in the presence of blood chimerism.

Adolescent↗
PubMed1997

Bilateral reduction mammoplasty in a patient treated with calcium channel blocker and cyclosporine after renal transplant: a case report.

A 28-year-old woman with end-stage renal disease secondary to diabetes mellitus and hypertension underwent cadaver renal transplant in April 1992. After surgery, she developed bilateral breast enlargement while she was taking cyclosporine for immunosuppression therapy and felodipine, a calcium channel blocker, for blood pressure control. She underwent bilateral reduction mammoplasty in June 1995 to treat progressive breast enlargement which interfered with her normal life activities. Through mechanisms only partially understood, calcium channel blockers and cyclosporine are reported to increase the serum prolactin level, producing gynecomastia in men. There is no report in current literature to support a similar phenomenon in women.

Adult↗
PubMed1997

Bacterial lipopolysaccharide stimulates the production of cytokines and the expression of costimulatory molecules by human peripheral blood dendritic cells: evidence for a soluble CD14-dependent pathway.

To investigate the responses of dendritic cells (DC) during Gram-negative infections, we analyzed the effects of graded doses of LPS on the cytokine profile, phenotype, and allostimulatory potential of human DC generated by culturing plastic-adherent PBMC in presence of IL-4 and granulocyte-macrophage-CSF. First, we found that LPS stimulates the production of high levels of TNF-alpha, IL-6, IL-8, IL-12 by DC and up-regulates their expression of HLA-DR, B7-1, B7-2, and CD40. The effects of LPS were dose dependent, with a significant stimulatory effect already observed at a concentration of 0.1 ng/ml and a plateau being reached at 10 ng/ml. These phenotypic changes correlated with increased allostimulatory properties of LPS-activated DC because DC treated with LPS were significantly more efficient than untreated DC in eliciting IL-2 and IFN-gamma synthesis by alloreactive T cells and stimulating their proliferation. Experiments using neutralizing anti-IL-12 mAb indicated that LPS-induced IL-12 is responsible for the increased production of IFN-gamma but not for the increased proliferation during MLR. Finally, we observed that the DC responses to low levels of LPS (1 ng/ml) were dramatically inhibited by a blocking anti-CD14 mAb, although DC do not express CD14 molecules on their membrane. Experiments using serum depleted of soluble CD14 (sCD14) and sCD14 either purified from human serum or in recombinant form further established that DC respond to LPS via a soluble CD14-dependent pathway.

Antigens, Surface↗
PubMed1997

Oxidation of ultrahigh molecular weight polyethylene characterized by Fourier Transform Infrared Spectrometry.

The effects of processing conditions, sterilization treatment, aging time, and poststerilization aging environment on the oxidation behavior of ultrahigh molecular weight polyethylene (UHMWPE) are examined. Oxidation is monitored by observing changes in the carbonyl peak appearing in Fourier Transform Infrared Spectrometry (FTIR) and is found to be relatively insensitive to processing conditions but strongly influenced by sterilization treatments and aging parameters. Oxygen uptake by UHMWPE increases as a result of gamma or electron beam irradiation and continues to rise during subsequent aging at a rate influenced by the aging environment. A hydrogen peroxide ambient causes more severe oxidation than either air or hyaluronic acid. Control (unsterilized) samples and those sterilized in ethylene oxide are resistant to oxidation under all conditions except hydrogen peroxide aging.

Biocompatible Materials↗
PubMed1997

Role of interleukin-4 and interleukin-10 in murine collagen-induced arthritis. Protective effect of interleukin-4 and interleukin-10 treatment on cartilage destruction.

OBJECTIVE: To examine the role of endogenous interleukin-4 (IL-4) and interleukin-10 (IL-10) and the therapeutic effect of the addition of IL-4 and IL-10 in early and established murine collagen-induced arthritis (CIA). METHODS: Murine recombinant IL-4, IL-10, or the combination was given intraperitoneally twice daily from the day of arthritis onset up to 7-10 days of CIA in DBA/1 mice. Anti-IL-4, anti-IL-10, or both antibodies were given intraperitoneally before or after the onset of CIA. The effect of cytokine or anticytokine treatment was monitored visually by macroscopic scoring. Histology and reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed at the end of the treatment period. RESULTS: IL-4 alone did not provoke any effect, IL-10 slightly suppressed the arthritis, but a more pronounced amelioration was found with the combination. This cooperative effect was noted after early treatment but also occurred when the start of treatment was delayed until 1 week after onset. Apart from suppression of macroscopic signs of inflammation, combined treatment with IL-4/IL-10 also reduced cellular infiltrates in the synovial tissue and caused pronounced protection against cartilage destruction. Moreover, levels of mRNA for tumor necrosis factor alpha (TNF alpha) and IL-1 were highly suppressed both in the synovial tissue and in the articular cartilage. In contrast, levels of IL-1 receptor antagonist (IL-1Ra) mRNA remained elevated, which suggests that the mechanism of protection may be related to suppressed production of TNF alpha and IL-1, with concomitant up-regulation of the IL-1Ra/IL-1 balance. However, accelerated onset of CIA and increased severity could be achieved with neutralizing anti-IL-10 antibodies. This expression could be further optimized with a combination of anti-IL-4 and anti-IL-10 antibodies, although anti-IL-4 alone was without effect. CONCLUSION: Our data are consistent with a dominant role of IL-10 in the natural suppression of arthritis expression, whereas combined treatment with IL-4 and IL-10 appears of potential therapeutic value, not only at the onset, but also in established arthritis.

Animals↗
PubMed1997

Interleukin-10 prevents the generation of dendritic cells from human peripheral blood mononuclear cells cultured with interleukin-4 and granulocyte/macrophage-colony-stimulating factor.

We evaluated the effects of interleukin (IL)-10 on the differentiation of dendritic cells (DC) obtained by culturing plastic-adherent peripheral blood mononuclear cells for 7 days in presence of granulocyte/macrophage-colony-stimulating factor (GM-CSF) + IL-4. The addition of IL-10 at the initiation of culture resulted in the generation of macrophage-like cells with expressing high levels of CD14 and decreased levels of CD1a and CD1c. Furthermore, cells generated in presence of IL-10 secreted lower levels of IL-12, but higher levels of IL-8 compared with DC generated in absence of IL-10, both spontaneously and after CD40 engagement. Finally, cells generated in presence of IL-10 were less efficient than DC in stimulating the production of IL-2, interferon-gamma, and IL-4 by allogeneic T cells. We conclude that IL-10 prevents the generation of DC induced by GM-CSF + IL-4 and favors the development of macrophages with a lower T cell stimulatory potential, but secreting higher levels of IL-8 than DC.

Antigens, CD↗
PubMed1997

Human dendritic cell responses to lipopolysaccharide and CD40 ligation are differentially regulated by interleukin-10.

We evaluated the effects of interleukin (IL)-10 on the maturation of human dendritic cells (DC) induced either by lipopolysaccharide (LPS) or CD40 engagement. For this purpose, DC generated by culturing plastic-adherent peripheral blood mononuclear cells for 7 days with granulocyte/macrophage-colony-stimulating factor and IL-4 were incubated for 3 days with either LPS (10 ng/ml) or 3T6 fibroblasts transfected with the gene encoding CD40 ligand, in absence or presence of IL-10. First we found that the membrane expression of CD83, a marker of mature DC, was inhibited by IL-10 when induced by LPS but not by CD40 engagement. Likewise, IL-10 inhibited LPS-induced but not CD40-dependent CD86 (B7.2) up-regulation on DC. Furthermore, IL-10 inhibited the production of IL-8 and tumor necrosis factor-alpha by DC when activated by LPS but not by CD40. In contrast, IL-10 inhibited IL-12 production in both activation systems. We conclude that IL-10 differentially influences LPS-dependent and CD40-dependent pathways of DC maturation.

Antigens, CD↗