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Biomedical subjects

M Goldman

Publications and source records attributed to M Goldman.

At least 145 records · Page 8Linked to original sources
PubMed1998

CD40 ligation prevents neonatal induction of transplantation tolerance.

To investigate the consequences of CD40 engagement on the neonatal induction of transplantation tolerance, BALB/c mice were injected at birth with (A/J x BALB/c) F1 spleen cells together with activating anti-CD40 mAb and grafted 4 wk later with A/J skin. Whereas A/J allografts were accepted in mice neonatally injected with F1 cells and control Ab, they were acutely rejected in mice injected with F1 cells and anti-CD40 mAb. Neonatal administration of anti-CD40 mAb resulted in enhanced anti-A/J CTL activity, increased IFN-gamma, and decreased IL-4 production by donor-specific T cells in vitro. Experiments using anti-cytokine mAb and IFN-gamma-deficient mice demonstrated that CD40 ligation prevents neonatal allotolerance through an IFN-gamma- and IL-12-dependent pathway. Finally, we found that newborn T cells express less CD40L than adult T cells upon TCR engagement. Taken together these data indicate that insufficiency of CD40/CD40L interactions contribute to neonatal transplantation tolerance.

Animals↗
PubMed1998

IL-12 prevents neonatal induction of transplantation tolerance in mice.

We investigated the effect of IL-12 on the induction of transplantation tolerance by neonatal injection of allogenic cells. We first observed that injection of newborn BALB/c mice with IL-12 and (A/J x BALB/c)F1 spleen cells prevented the Th2 alloimmune response induced by neonatal inoculation of F1 cells alone and allowed the differentiation of T cells secreting high amounts of IL-2 and IFN-gamma in mixed lymphocyte cultures with donor-type stimulators. Furthermore, IL-12 administration resulted in the emergence of anti-donor cytotoxic T lymphocyte responses although at lower levels than in control uninjected mice. In parallel, we found that mice injected at birth with IL-12 and F1 cells did not develop chimerism and were able to reject a donor-type skin graft as efficiently as control mice. We conclude that IL-12 inhibits the Th2 polarization of the newborn response to alloantigens and prevents thereby the establishment of transplantation tolerance.

Animals↗
PubMed1998

Oxidative stress up-regulates IL-8 and TNF-alpha synthesis by human dendritic cells.

In addition to their damaging effects, reactive oxygen intermediates exert a regulatory role on gene expression and cell apoptosis. In this study, we evaluated the effects of oxidative stress on human dendritic cells (DC), a cell type which is critical for the initiation of the immune response. For this purpose, we tested the effects of H2O2 on DC derived from adherent peripheral blood mononuclear cells cultured in the presence of granulocyte-macrophage colony-stimulating factor and IL-4. Despite a moderate increase of DC apoptosis in the presence of H2O2, we observed that H2O2 stimulated the production of IL-8 and TFN-alpha by DC in a dose-dependent manner. The induction of cytokine synthesis was found to depend on the oxidative properties of H2O2 as it was inhibited by the addition of catalase, and to require de novo protein synthesis as it was not observed in the presence of cycloheximide. These data suggest that DC could contribute to innate immunity through an enhanced production of inflammatory cytokines in response to oxidative stress.

Cell Survival↗
PubMed1998

Interleukin-10 controls neutrophilic infiltration, hepatocyte proliferation, and liver fibrosis induced by carbon tetrachloride in mice.

The role of the anti-inflammatory cytokine interleukin-10 (IL-10) was investigated in the mouse model of liver injury induced by carbon tetrachloride (CCl4). To address the role of endogenous IL-10 production, acute hepatitis was induced by CCl4 in C57Bl/6 IL-10 gene knock out (KO) and wild-type (WT) mice. After CCl4 challenge, serum and liver levels of tumor necrosis factor-alpha (TNF-) and serum levels of transforming growth factor-beta 1 (TGF-beta1) increased and were significantly higher in IL-10 KO mice, whereas IL-6 serum levels were only slightly increased compared with WT mice. At histological examination, the livers disclosed a significantly more prominent neutrophilic infiltration in IL-10 KO mice 12 and 24 hours after CCl4 injection. In contrast, hepatocyte necrosis, evaluated by histological examination and serum alanine aminotransferase levels, was only marginally affected. The proliferative response of hepatocytes, assessed by the proliferating cell nuclear-antigen labeling index, was significantly increased in IL-10 KO mice, compared with WT mice 48 hours after CCl4 injection. Finally, repeated CCl4 injections led to more liver fibrosis in IL-10 KO mice after 7 weeks. In conclusion, endogenous IL-10 marginally affects the hepatocyte necrosis although it controls the acute inflammatory burst induced by CCl4. During liver repair, it limits the proliferative response of hepatocytes and the development of fibrosis.

Animals↗
PubMed1998

A pharmacokinetic study of intravenous itraconazole followed by oral administration of itraconazole capsules in patients with advanced human immunodeficiency virus infection.

A randomized, open-label, comparative study was conducted in 30 male patients with moderately advanced human immunodeficiency virus (HIV) infection to examine the pharmacokinetics of an investigational intravenous preparation of itraconazole compared with pharmacokinetics after administration of itraconazole capsules. The study also assessed whether adequate plasma concentrations of itraconazole could be rapidly achieved with the intravenous formulation and then maintained after cessation of intravenous therapy with itraconazole capsules. All patients received 200 mg intravenous itraconazole as a 1-hour infusion in 40% hydroxypropyl-beta-cyclodextrin (HP-beta-CD) vehicle twice daily for 2 days, and then 200 mg intravenously once daily for 5 days. Patients then received itraconazole capsules, either 200 mg twice daily or 200 mg once daily for 28 days. Steady-state plasma concentrations of itraconazole were reached by day 3 with intravenous infusion, a much shorter time than observed with administration of itraconazole capsules. Steady-state concentrations of itraconazole and hydroxyitraconazole were effectively maintained during the rest of the intravenous infusions of itraconazole. Oral follow-up with administration of 200-mg capsules once daily could not maintain the plasma concentrations of itraconazole and hydroxyitraconazole obtained at the end of the intravenous treatment, whereas twice-daily oral administration maintained or increased these concentrations. Mean plasma concentrations of itraconazole and hydroxyitraconazole on day 7 were similar to those on day 36 in the twice-daily group. Mean renal clearance was comparable to mean total body clearance, and approximately 93% to 101% of the HP-beta-CD was excreted unchanged in urine within 12 hours of administration. The HP-beta-CD was essentially eliminated through the kidney, and little accumulation in the body was observed in this patient population. Adverse events during the intravenous phase were most commonly associated with intravenous administration. Intravenous infusion of itraconazole for 7 days followed by administration of itraconazole capsules twice daily for 28 days is an effective dose regimen in patients with advanced HIV infection.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1998

Goal-directed transesophageal echocardiography performed by intensivists to assess left ventricular function: comparison with pulmonary artery catheterization.

OBJECTIVES: Transesophageal echocardiography (TEE) is a valuable procedure for assessing left ventricular (LV) function, but it has not been widely applied in critical care because of the limited number of intensivists who are trained in echocardiography. This prospective study was designed to evaluate the feasibility of training intensivists to perform a goal-directed, limited-scope TEE to assess LV function in critically ill patients using a pediatric monoplane TEE probe. A secondary goal was to compare the usefulness of the TEE data with that of data obtained by a simultaneous pulmonary artery catheter (PAC). DESIGN: Prospective, blinded. SETTING: University teaching hospital. PARTICIPANTS: One hundred consecutive, intubated, intensive care unit patients. INTERVENTIONS: Five surgical intensivists with no previous background in echocardiography were trained under the supervision of two cardiologists to perform limited-scope TEE using a monoplane pediatric probe. One intensivist (A) reviewed the PAC data and recorded a diagnostic impression and therapeutic plan. A second intensivist (B), blinded to the PAC data, then performed TEE to determine cardiac volume, LV wall thickness, and LV global and regional wall motion. Intensivists A and B reviewed the data from both PAC and TEE, and intensivist A then formulated a new diagnosis and therapeutic plan. MEASUREMENTS AND MAIN RESULTS: Intensivists performed 48 TEE examinations under direct supervision of a cardiologist, and 52 without supervision, but reviewed poststudy. The average duration of TEE was 12 +/- 7 minutes. The intensivists' interpretations of TEE data were deemed correct in 93% of cases for LV wall thickness, 87% for intracardiac volume status, 81% for regional LV wall motion abnormalities, and 77% for global LV function. When the TEE and PAC technologies were compared, it was found that the TEE data disagreed with the PAC evaluation of intracardiac volume in 55% of cases and with the PAC assessment of myocardial function in 39% of cases. The post-PAC therapeutic recommendations were different from the post-TEE therapeutic recommendations in 58% of patients. CONCLUSIONS: Training intensivists in limited-scope, goal-directed TEE, using a pediatric monoplane probe to evaluate LV function, can be done rapidly and safely, and yield data pertinent to management of critically ill patients even in the early stages of skill acquisition.

Adult↗
PubMed1998

The influence of sterilization technique and ageing on the structure and morphology of medical-grade ultrahigh molecular weight polyethylene.

The effects of four sterilization treatments (gamma radiation in nitrogen, electron-beam radiation, ethylene oxide gas, and no sterilization) on the structure and morphology of ultrahigh molecular weight polyethylene (UHMWPE) were monitored as a function of ageing time in air for a period of 1.5 y. Characterization techniques employed include differential scanning calorimetry, density gradient column, transmission electron microscopy, and small-angle X-ray scattering. Ethylene oxide gas does not affect the structure of the polymer. Both forms of radiation lead to measurable alterations of the material's structure, including an increase in crystallinity, an increase in density, and the enhancement of lamellae crystalline stacking. Most changes in structure occur in the first few months with little differences observed upon subsequent ageing in air. The sharpness of the crystalline-amorphous boundaries decreases with time for irradiated UHMWPE and is believed to be linked to the oxidation of the polymer.

Journal Article↗
PubMed1998

IL-10 up-regulates nitric oxide (NO) synthesis by lipopolysaccharide (LPS)-activated macrophages: improved control of Trypanosoma cruzi infection.

We examined the effects of IL-10 on tumour necrosis factor-alpha (TNF-alpha) and NO production by LPS-activated macrophages and on the ability of these cells to control Trypanosoma cruzi infection. We first observed that the addition of rIL-10 to macrophages of the J774 cell line decreased their synthesis of TNF-alpha but increased their release of NO in a dose-dependent manner. In parallel, treatment of J774 cells with rIL-10 resulted in a better control of T. cruzi infection involving up-regulation of NO synthesis, as it was not observed in presence of N-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase. The enhancing effect of rIL-10 on NO production was not observed on peritoneal macrophages from wild-type C57Bl/6 mice, but well on macrophages from IL-10 knock-out mice. The control of NO production by endogenous IL-10 was confirmed by the demonstration that neutralization of IL-10 secreted by LPS-activated macrophages from wild-type mice inhibited their production of NO and, in parallel, their ability to control T. cruzi infection. Taken together, these data demonstrate that both exogenous and endogenous IL-10 up-regulate the production of NO by LPS-activated macrophages and improve thereby their ability to clear T. cruzi infection.

Animals↗
PubMed1998

Randomized, double-blind clinical trial of amphotericin B colloidal dispersion vs. amphotericin B in the empirical treatment of fever and neutropenia.

We conducted a prospective, randomized, double-blind study comparing amphotericin B colloidal dispersion (ABCD) with amphotericin B in the empirical treatment of fever and neutropenia. Patients with neutropenia and unresolved fever after > or = 3 days of empirical antibiotic therapy were stratified by age and concomitant use of cyclosporine or tacrolimus. Patients were then randomized to receive therapy with ABCD (4 mg/[kg.d]) or amphotericin B (0.8 mg/[kg.d]) for < or = 14 days. A total of 213 patients were enrolled, of whom 196 were evaluable for efficacy. Fifty percent of ABCD-treated patients and 43.2% of amphotericin B-treated patients had a therapeutic response (P = .31). Renal dysfunction was less likely to develop and occurred later in ABCD recipients than in amphotericin B recipients (P < .001 for both parameters). Infusion-related hypoxia and chills were more common in ABCD recipients than in amphotericin B recipients (P = .013 and P = .018, respectively). ABCD appeared comparable in efficacy with amphotericin B, and renal dysfunction associated with ABCD was significantly less than that associated with amphotericin B. However, infusion-related events were more common with ABCD treatment than with amphotericin B treatment.

Adolescent↗
PubMed1998

Central nervous system infections due to Stomatococcus mucilaginosus in immunocompromised hosts.

We present a case of central nervous system (CNS) infection due to Stomatococcus mucilaginosus involving a patient with leukemia and summarize 12 additional published reports of CNS infection due to this organism in immunocompromised hosts. The infection was diagnosed most commonly in the setting of hematologic malignancy accompanied by chemotherapy-induced neutropenia. S. mucilaginosus was recovered from blood prior to discovery of the CNS infection in 62% of cases. Signs or symptoms of CNS infection were observed in all patients. Although a number of patients responded to regimens containing intravenous vancomycin, the addition of intrathecal vancomycin appeared to be of benefit in some cases.

Central Nervous System Infections↗
PubMed1998

Bacterial extract OM85-BV induces interleukin-12-dependent IFN-gamma production by human CD4+ T cells.

To obtain insight into the possible mode of action of bacterial extracts used as immunostimulants in Europe, we used the ELISPOT technique to investigate the effects of one of them (OM85-BV, Broncho-Vaxom) on interferon-y (IFN-gamma) production by peripheral blood mononuclear cells (PBMC). We found that (1) OM85-BV stimulates IFN-gamma secretion by PBMC from normal individuals and human immunodeficiency virus (HIV)-infected patients, (2) CD4+ cells represent the major source of IFN-gamma produced in response to OM85-BV, and (3) this effect of OM85-BV involves the induction of interleukin-12 (IL-12) secretion by accessory cells. We conclude that bacterial extracts might enhance antimicrobial defenses by eliciting IL-12-dependent IFN-gamma synthesis by CD4+ T cells.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Isolation and infusion of donor CD34+ bone marrow cells in cadaver kidney transplantation.

BACKGROUND: Infusion of donor bone marrow cells induces tolerance in allograft models. CD34+ stem cells present in human bone marrow could be endowed with tolerogenic properties. METHODS: CD34+ stem cells were isolated from bone marrow extracted from vertebral bodies of cadaveric donors. Donor CD34+ cells (0.6-3.7 x 10(6)/kg) were infused during surgery in 10 kidney transplant recipients receiving OKT3 as induction therapy. Chimerism was investigated using nested PCR for donor-specific HLA alleles. RESULTS: The infusion of CD34+ stem cells was perfectly tolerated. Five patients remained free of acute rejection at follow-up, 47-325 days post-operatively. The five other patients underwent a single episode of corticosensitive acute rejection. Long-term chimerism was not induced in the seven patients investigated for the persistence of donor DNA. CONCLUSIONS: Infusion of donor CD34+ stem cells in kidney transplantation is safe. The clinical usefulness of the procedure remains to be established.

Adult↗
PubMed1998

Spontaneous secretion of interferon gamma and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes.

BACKGROUND: Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses. AIMS: To quantify interferon gamma (IFN-gamma) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation. PATIENTS: Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa. METHODS: Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-gamma and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT). RESULTS: The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-gamma (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-gamma SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-gamma and IL-4 were mainly produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-gamma in the basal state, and 0.1% secreted IL-4. CONCLUSIONS: Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-gamma and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases.

Adult↗