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Biomedical subjects

M Goldman

Publications and source records attributed to M Goldman.

At least 325 records · Page 18Linked to original sources
PubMed1993

Increased IL-6 production and IL-6-mediated Ig secretion in murine host-vs-graft disease.

BALB/c mice neonatally injected with semiallogenic (A/J x BALB/c)F1 splenocytes develop a host-vs-graft (HVG) reaction between host T cells and donor B cells, resulting in hypergammaglobulinemia, splenomegaly, and increased serum levels of various autoantibodies. This syndrome is associated with a polyclonal activation of the donor-derived B cells. High serum levels of IL-6 were found in 4-wk-old mice undergoing HVG disease (mean +/- SEM, 132 +/- 93 as compared with 12 +/- 2 in control mice, p < 0.05). Also supernatants of spleen cell cultures from HVG mice contained increased levels of IL-6. In situ hybridization and cell depletion experiments demonstrated that host macrophages were responsible for this pathologic IL-6 secretion. The spontaneous in vitro production of autoreactive antibodies by donor B cells from HVG mice was further enhanced by adding human rIL-6, whereas addition of human rIL-1 beta, human rIL-2, murine rIL-4, murine rIL-5, or combinations of these cytokines had no effect. Finally, addition of blocking anti-IL-6 and anti-IL-6 receptor mAb markedly reduced hyper IgG1 production in cultures of spleen cells from HVG mice. These data suggest that an increased production of IL-6 by persistently stimulated host macrophages is involved in the activation of donor B cells leading to HVG disease.

Animals↗
PubMed1993

Breast cancer risk in mothers of multiple births.

Data from an international case-control study of breast cancer that was conducted in the 1960s were used to examine whether multiple births affect the risk of breast cancer in the mother. Among 2821 parous breast-cancer patients, 88 had had one or more multiple births, whereas among 8882 controls 247 had had one or more multiple births; the logistic-regression-adjusted odds ratio (OR) was 1.21, the 95% confidence interval (CI), 0.94 to 1.55. The OR was significantly elevated during the 15-year period following the latest multiple birth (1.76; CI, 1.12 to 2.75), but declined toward the null afterwards. A late first pregnancy imparted a substantially higher breast-cancer risk when it was multiple rather than singleton; the OR was 2.34 for a multiple and 1.48 for a singleton first pregnancy when the cutoff point was 30 years, and 4.58 and 1.57, respectively, when the cutoff point was 35 years. Since multiple pregnancies are characterized by higher levels of pregnancy estrogens, the results of this study would be compatible with the hypothesis that these hormones may be responsible for the transient increase in breast-cancer risk following a term pregnancy and, in particular, a multiple term pregnancy. The long-term reduction of breast-cancer risk is probably due to a different mechanism, most likely the terminal differentiation of susceptible mammary-gland cells.

Adult↗
PubMed1993

Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia.

Because of its ability to efficiently inhibit in vitro cytokine production by activated macrophages, we hypothesized that interleukin (IL) 10 might be of particular interest in preventing endotoxin-induced toxicity. We therefore examined the effects of IL-10 administration before lipopolysaccharide (LPS) challenge in mice. A marked reduction in the amounts of LPS-induced tumor necrosis factor (TNF) release in the circulation was observed after IL-10 pretreatment at doses at low as 10 U. IL-10 also efficiently prevented the hypothermia generated by the injection of 100 micrograms LPS. Finally, pretreatment with a single injection of 1,000 U IL-10 completely prevented the mortality consecutive to the challenge with 500 micrograms LPS, a dose that was lethal in 50% of the control mice. We conclude that IL-10 inhibits in vivo TNF secretion and protects against the lethality of endotoxin in a murine model of septic shock.

Animals↗
PubMed1993

In vivo induction of interleukin 10 by anti-CD3 monoclonal antibody or bacterial lipopolysaccharide: differential modulation by cyclosporin A.

We investigated the in vivo effects of cyclosporin A (CsA) on the production of interleukin (IL) 10, a cytokine with major immunosuppressive properties. To elicit IL-10 production in vivo, BALB/c mice were injected either with the anti-mouse CD3 145-2C11 monoclonal antibody (mAb) (25 micrograms) or with bacterial lipopolysaccharide (LPS) (20 micrograms). A systemic release of IL-10 was observed in both models, IL-10 serum levels reaching 1.60 +/- 0.32 U/ml (mean +/- SEM) and 0.67 +/- 0.09 U/ml 6 h after injection of 145-2C11 mAb and LPS, respectively. Experiments in nude mice indicated that T cells are involved in the induction of IL-10 by anti-CD3 mAb, but not by LPS. Pretreatment with CsA (total dose: 50 mg/kg) before injection of 145-2C11 mAb completely prevented the release of IL-10 in serum as well as IL-10 mRNA accumulation in spleen cells. In contrast, CsA markedly enhanced LPS-induced IL-10 release (IL-10 serum levels at 6 h: 8.31 +/- 0.43 vs. 0.71 +/- 0.15 U/ml in mice pretreated with CsA vehicle-control, p < 0.001), as well as IL-10 mRNA accumulation in spleen. We conclude that CsA differentially affects IL-10 production in vivo depending on the nature of the eliciting agent. This observation might be relevant to clinical settings, especially in organ transplantation.

Animals↗
PubMed1993

Diaphragm function is not impaired by pneumoperitoneum after laparoscopy.

Open cholecystectomy is known to induce a major restrictive respiratory syndrome. These respiratory disturbances, although of reduced magnitude, still persist after laparoscopic cholecystectomy. To determine the role of pneumoperitoneum per se in the respiratory dysfunction observed after this procedure, seven patients were studied before and 2 hours after laparoscopy. This diagnostic procedure avoids the upper midline incision and the surgical injury of cholecystectomy. Ventilatory performance and diaphragm function were assessed as follows: (1) during quiet tidal breathing by obtaining measurements of esophageal, gastric, and transdiaphragmatic pressures; determining the ratio of gastric pressures to esophageal pressures; and abdomen-rib cage partitioning of tidal volume obtained from two differential linear transformers and (2) during maximal respiratory efforts by obtaining measurements of vital capacity and maximal transdiaphragmatic pressure during Müller's maneuver and a sniff test. Although a large residual pneumoperitoneum (assessed as the maximal height of the suprahepatic space: Hmax = 30.3 +/- 7.8 mm) was observed after laparoscopy, we did not find any change suggestive of diaphragm dysfunction. We thus conclude that postoperative residual pneumoperitoneum per se is unable to explain the diaphragm dysfunction observed after open or laparoscopic cholecystectomy.

Cholecystectomy, Laparoscopic↗
PubMed1993

T helper type 2-like cells and therapeutic effects of interferon-gamma in combined immunodeficiency with hypereosinophilia (Omenn's syndrome).

We characterized the defects of CD4+ cells in a 17-month-old girl suffering from combined immunodeficiency with hypereosinophilia (Omenn's syndrome). Because the vast majority of peripheral blood CD4+ cells expressed the CD45R0 isoform, we purified circulating CD4+ CD45R0+ cells from the patient and healthy individuals in order to compare their production of cytokines. The patient's CD4+ CD45R0+ cells spontaneously produced high levels of interleukin-5 (IL-5) in vitro (1600 pg/ml after 24 h of culture) and this was associated with the presence of IL-5 in serum (323 pg/ml). After stimulation with phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187, they produced higher levels of IL-4 (306 vs. 55 +/- 4 pg/ml) and IL-5 (2900 vs. 213 +/- 72 pg/ml) and lower levels of IL-2 (17 vs. 63 +/- 17 IU/ml) and interferon-gamma (IFN-gamma) (16 vs. 299 +/- 70 IU/ml) than controls CD4+ CD45R0+ cells. This T helper type 2 (Th2) pattern was confirmed by the detection using reverse polymerase chain reaction of IL-4, IL-5 and IL-10 mRNA within peripheral blood mononuclear cells. During a therapeutic trial with human IFN-gamma (40 micrograms/day) which ameliorated the clinical status of the patient, we observed a down-regulation of the in vivo expression of IL-5 and IL-10, a normalization of the eosinophil count and an improvement of the T cell response to phytohemagglutinin. This observation indicates for the first time that Th2-like cells might be involved in certain forms of congenital immunodeficiency and that IFN-gamma might down-regulate their activities in vivo.

CD4 Antigens↗
PubMed1993

Interleukin-10 inhibits the induction of monocyte procoagulant activity by bacterial lipopolysaccharide.

Monocytes stimulated with bacterial lipopolysaccharide (LPS) generate a procoagulant activity (PCA) related to the induction of tissue factor (TF) expression at their surface. Since interleukin-10 (IL-10) was recently shown to inhibit LPS-induced cytokine production and is currently considered as a potential therapeutic agent in septic shock, we were interested to determine its effects on LPS-induced monocyte PCA. Peripheral blood mononuclear cells (PBMC) from healthy donors were incubated with 1 microgram/ml LPS in the presence of serial dilutions of recombinant human IL-10 and PCA was determined after 6 h in a one-stage clotting assay. IL-10 inhibited in a dose-dependent manner LPS-induced TF-dependent PCA: a significant effect was already observed with 30 pg/ml IL-10 while 64-97% inhibition was achieved with 120 pg/ml IL-10. In parallel flow cytometry experiments, IL-10 was shown to block LPS-induced TF expression at the surface of monocytes. In order to inhibit LPS-induced PCA, IL-10 had to be added to PBMC at least 6 h before LPS challenge. This inhibitory effect of IL-10 was already apparent at the TF mRNA level and was prevented by co-incubation with cycloheximide (20 micrograms/ml). These data suggest that IL-10 acts via the induction of protein(s) which might interfere with TF gene transcription or mRNA stability. We conclude that the protective effects of IL-10 in endotoxinemia might be related not only to cytokine synthesis blockade but also to inhibition of LPS-induced PCA.

Base Sequence↗
PubMed1993

TH2 activated cells prevent experimental autoimmune uveoretinitis, a TH1-dependent autoimmune disease.

Mercuric chloride (HgCl2) injections protect (Lewis x Brown-Norway) F1 (F1) rats against experimental autoimmune uveoretinitis (EAU) induced by immunization with the retinal S antigen (S-Ag); in contrast HgCl2-injected F1 rats develop EAU following transfer of lymph node (LN) cells from rats immunized with S-Ag alone. In the present study we demonstrate that the ability of LN cells from rats protected against EAU to transfer the disease into naive F1 rats was considerably reduced. These LN cells neither produced interleukin (IL)-2 nor (interferon (IFN)-gamma but exhibited mRNA for IL-4. In contrast, LN cells from diseased rats easily transferred EAU into naive F1 rats, produced significant IL-2 and IFN-gamma levels but barely exhibited mRNA for IL-4. Furthermore protected rats predominantly produced IgG1 anti-S-Ag antibodies, while diseased rats produced IgG2b anti-S-Ag antibodies and the increase in expression of MHC class II molecules on B cells was higher in protected rats than in diseased rats. These data suggest that (1) to exert a protective effect, HgCl2 must act at an early stage of differentiation of precursors of S-Ag specific T cells, and (2) this effect is related to the preferential activation of TH2 cells to the detriment of uveitogenic TH1 cells. Finally, these results indicate that activation of TH2 cells protect from a TH1-dependent autoimmune disease.

Animals↗
PubMed1993

Blastomycosis of the skull base.

Blastomycosis is usually considered a pulmonary or cutaneous disease. A patient with blastomycosis of the infratemporal fossa temporal bone and sinuses without pulmonary disease is presented. Extensive skull base involvement required surgical debridement for relief of pain, and long-term systemic antifungal therapy. The literature is reviewed and discussed.

Journal Article↗
PubMed1993

IL-5 in post-traumatic eosinophilic pleural effusion.

Thoracic trauma or pneumothorax can result in pleural fluid eosinophilia. In this study we investigated the role of the eosinophilopoietic cytokine IL-5 in three cases of post-traumatic eosinophilic pleural effusions (EPE). Using a specific immunoenzymatic assay, significant levels of IL-5 were found in EPE (range 100-3000 pg/ml), while IL-5 was undetectable (< 25 pg/ml) in corresponding serum samples and in non-eosinophilic pleural fluids. IL-5 present in pleural fluids was found bioactive in a proliferative assay using a mouse CTLL-2 cell line transfected with the cDNA corresponding to the alpha chain of the human IL-5 receptor. Using a reverse polymerase chain reaction (PCR) method, we found IL-5 mRNA expression within pleural mononuclear cells from patients with EPE, but not in corresponding peripheral blood mononuclear cells (PBMC), confirming that IL-5 is synthesized locally in the pleural cavity. In the two cases in which pleural CD4+ cells were purified, these cells were identified as the major source of IL-5. Taken together, these data indicate that the development of post-traumatic EPE is related to a local secretion of IL-5 by CD4+ cells present in the pleural cavity.

Aged↗
PubMed1993

Effect of breathing pattern on blood pressure and heart rate oscillations in humans.

1. The relationships of respiratory sinus arrhythmia (RSA) and respiratory changes in systolic blood pressure (SBP) to tidal volume (VT) and breathing frequency (BF), were quantified during voluntary control of VT and BF in healthy subjects. 2. Respiration was measured non-invasively with a respiratory inductive plethysmograph, which was calibrated prior to each study while breathing through a pneumotachygraph. Finger arterial blood pressure was measured non-invasively by the Finapres. 3. Heart rate (HR) increased during inspiration, with a nearly fixed time delay for most VT and BF approximating 0.9 s. The magnitude of RSA increased with increases in VT and with decreases in BF. SBP decreased during inspiration, with a time delay which increased as BF decreased, resulting in a phase delay approximating 160 degrees. The magnitude of the inspiratory fall in SBP increased with increases in VT. Increased amplitudes of RSA and SBP variation occurred at the lowest BF, consistent with the possibility of interactions between respiratory-related influences and those due to 'slow waves' of vasomotor tone. 4. The present results are consistent with the conclusion that respiratory effects on SBP are caused by a mechanism other that simply changes in HR.

Adult↗
PubMed1993

Impaired phagocyte responses to lipopolysaccharide in paroxysmal nocturnal hemoglobinuria.

Bone marrow-derived cells from patients suffering from paroxysmal nocturnal hemoglobinuria (PNH) show a defect in the expression of phosphatidylinositol-anchored membrane proteins, including the CD14 molecule. Blocking experiments with anti-CD14 monoclonal antibodies have shown that lipopolysaccharide (LPS)-induced tumor necrosis factor alpha production by monocytes depends on the interaction between CD14 and a complex formed by LPS and LPS-binding protein. We used a whole-blood model to examine the LPS-induced production of tumor necrosis factor alpha and interleukin-6 in PNH patients and healthy volunteers. At low endotoxin concentrations (1 ng/ml), PNH patients displayed a marked defect in the production of both cytokines, whereas at high LPS concentrations (100 ng/ml), cytokine production was similar to that in healthy volunteers. Using flow cytometry, we also studied the expression of the adhesion molecules Mac-1 (CD11b/CD18) and ICAM-1 (CD54) by monocytes and granulocytes after LPS stimulation. Compared with phagocytes from healthy volunteers, CD14-deficient cells showed poor Mac-1 and ICAM-1 upregulation when whole blood was stimulated with LPS (1 ng/ml), whereas their response to higher LPS doses (100 and 1,000 ng/ml) was essentially normal. The importance of the CD14 molecule in the activation of phagocytes by low LPS concentrations was confirmed by the inhibitory effect of an anti-CD14 antibody both in healthy volunteers and in PNH patients. Since these patients produce the soluble form of the CD14 molecule, these data suggest that soluble CD14 could play a role in phagocyte responses to LPS. We conclude that, in whole blood, phagocytes from PNH patients show impaired responsiveness to LPS and this phenomenon is most probably related to their defect in expression of membrane CD14.

Antigens, CD↗
PubMed1993

Induced abortions, miscarriages, and tobacco smoking as risk factors for secondary infertility.

STUDY OBJECTIVE: The aim was to determine whether induced abortions could increase the risk of secondary infertility. DESIGN: This was a case-control study; cases were women with secondary infertility, individually matched to two controls who were currently pregnant. Each participant was interviewed by one of two medical doctors using a questionnaire that sought information on their demographic, socioeconomic, medical, and reproductive status. The data were analysed by conditional logistic regression. SETTING: The study took place in the Alexandra Maternity Hospital in Athens, Greece, in 1987-88. PARTICIPANTS: 84 women consecutively admitted with secondary infertility and 168 pregnant controls took part. MAIN RESULTS: Eight cases and no controls reported a previous ectopic pregnancy, confirming that the occurrence of a pregnancy of this type dramatically increases the risk of secondary infertility. Furthermore, the occurrence of either induced abortions or spontaneous abortions independently and significantly increased the risk of subsequent development of secondary infertility. The logistic regression adjusted relative risks (and 95% confidence intervals) for secondary infertility were 2.1 (1.1-4.0) when there was one previous induced abortion and 2.3 (1.0-5.3) when there were two previous induced abortions. Tobacco smoking significantly increased the risk of secondary infertility, the adjusted relative risk being 3.0 (1.3-6.8). CONCLUSIONS: Legalised induced abortions, as currently practised in Greece, appear to increase slightly the relative risk of secondary infertility.

Abortion, Induced↗
PubMed1993

Parental history of early myocardial infarction is associated with decreased levels of lipoparticle AI in adolescents.

A family history of coronary heart disease (CHD) is a known risk factor for CHD. To investigate the possible role of lipoprotein particles in the relationship between family history of CHD and risk of CHD, we performed a case-control study in a sample of adolescents. The case group consisted of 97 adolescents whose parents had suffered a verified myocardial infarction before the age of 55 years. The control group was composed of 194 subjects without any family history of CHD. One case patient was matched to two control subjects for gender, age, and body mass index. In both groups, plasma lipid variables were measured, including total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) low-density lipoprotein cholesterol, apolipoprotein (apo)AI, apoB, apoAI-containing lipoprotein particles without apoAII (LpAI) and with apoAII, and apoB-containing lipoprotein particles with apoE and with apoCIII. Adolescents with a family history of early myocardial infarction had lower plasma levels of HDL-C (P < .0001), apoAI (P < .01), and LpAI (P < .0001) than control subjects (adjusted for gender, age, body mass index, smoking habits, and oral contraceptive use). No other differences were statistically significant between case and control subjects. The analysis was repeated separately for male and female subjects. In young men, the best predictor of family history of early myocardial infarction was the LpAI plasma level, whereas in young women it was the HDL-C plasma level. Decreased levels of HDL-C and LpAI lipoprotein particles explain part of the relationship between parental history of early myocardial infarction and CHD risk.

Adolescent↗