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M Goldman

Publications and source records attributed to M Goldman.

At least 361 records · Page 20Linked to original sources

Lipopolysaccharide induces up-regulation of CD14 molecule on monocytes in human whole blood.

We examined by flow cytometry the expression of lipopolysaccharide (LPS) receptor CD14 molecule on monocytes after addition of LPS to human whole blood. Within 30 min LPS induced an increase in monocyte CD14 expression, peaking between 1 and 3 h and followed by a slow decrease. Maximal increase in anti-CD14 monoclonal antibody binding sites was estimated as twofold the basal value. This effect, already observed with very low concentrations of LPS (10 pg/ml), was dose dependent. Protein synthesis was not involved in the CD14 hyperexpression since it was not influenced by co-incubation with cycloheximide. Finally, LPS-induced up-regulation of monocyte CD14 was associated with an increased binding of fluoresceinated LPS. We conclude that LPS in whole blood up-regulates the expression of its own CD14 receptor on monocytes, a phenomenon that could be relevant to the pathogenesis of gram-negative sepsis.

Antigens, CD↗

High or low dose steroid therapy for acute renal transplant rejection after prophylactic OKT3 treatment: a prospective randomized study.

In this prospective randomized study, acute renal transplant rejections occurring in patients who received prophylactic OKT3 therapy were treated with either 3 pulses of 8 mg/kg methylprednisolone (MPS) in an alternate-day regimen (total dose 25 mg/kg in 1 week, H group, n = 24) or 5 daily pulses of 3 mg/kg MPS (total dose 17 mg/kg, L group, n = 22). Acute rejection was proven by biopsy in more than 85% of cases in both groups. No difference was observed in rejection reversal (H 88%, L 91%), graft losses in the following 3 months (H 11%, L 4%) or the time evolution of the serum creatinine levels. The number (H 14, L 21) as well as the nature and severity of infections were similar in both groups. Only one death occurred in a patient who received OKT3 rescue therapy for corticoresistant rejections and developed Epstein-Barr virus (EBV)-related lymphoma. In conclusion, low dose MPS pulses appear as effective and safe as a higher dose to reverse acute rejection occurring after OKT3 prophylaxis. Thus, we favour the use of the low dose regimen in these patients.

Acute Disease↗

Detrimental role of donor-recipient HLA-DQ5 and -DQ6 disparities on cadaver kidney graft survival.

Donor-recipient incompatibility (D + R -) for HLA-DQ1, but not for -DQ2 or -DQ3, is associated with an adverse effect on cadaver kidney graft survival. Until now, however, DQ1 recipients of DQ1-negative kidneys (D - R +) have not been differentiated from DQ1-identical donor-recipient pairs (D + R +) and splits of DQ1, DQ5 and DQ6, have not been studied in that respect. From our data (480 transplantations performed from January 1980 to December 1990), three donor-recipient DQ combinations (D + R +, D - R +, D + R -) were formed for each of four DQ specificities (DQ2, DQ3, DQ5, DQ6). As DR-DQ linkage disequilibrium is well conserved in caucasoid individuals, DQ specificities were inferred from the associated DR specificities. Graft survival rate (%) was significantly lower for the DQ5 D + R - and the DQ6 D - R + combinations when compared with the other corresponding DQ combinations, whereas no significant difference was observed between the DQ2 and DQ3 combinations. In conclusion, if DQ1 plays a prominent role in kidney graft survival, the effects of its splits appear dissociated: DQ5 could be a marker of high antigenicity and DQ6 a marker of high responsiveness.

Cadaver↗

Kinetics of action of salbutamol inhaled from a metered dose inhaler (MDI) and a "Diskhaler".

In a double-blind cross-over study, 12 patients with reversible airways obstruction were treated with 200 micrograms salbutamol base in aerosol or 400 micrograms of powder following methacholine-induced bronchoconstriction. Salbutamol was inhaled either from a conventional metered dose inhaler (MDI) or from an inhaler (Diskhaler) utilizing the powdered form of the drug. The efficacy of both forms was identical whether assessed in terms of FEV1 or vital capacity. The ratio of the increase in FEV1 or vital capacity after bronchodilatation to the decrease during the prior bronchoconstriction was 1.4, indicating that both FEV1 and vital capacity improved over baseline following bronchodilatation. In six subjects, the onset of action of the powder form was more rapid, and in four the MDI acted more rapidly. In the group as a whole, the mean time constant for the action of salbutamol was identical (3.8 min) for the two forms. It is concluded that salbutamol powder has a similar efficacy and time course of action as the aerosol, probably because both formulations produce similar sized particles of the drug.

Administration, Inhalation↗

Effect of dietary fiber on colonic bacterial enzymes and bile acids in relation to colon cancer.

Because of the potential significance of colonic bacteria and secondary bile acids in the pathogenesis of colon cancer, the present study investigated the effect of different types of dietary fiber on fecal bacterial enzymes, namely, beta-glucuronidase, 7 alpha-dehydroxylase, nitroreductase, and azoreductase, and on bile acids and neutral sterols in premenopausal women. The subjects consumed 13-15 g of wheat, oat, or corn bran daily for 8 weeks in addition to their normal diet. Stools collected during the normal and fiber diet periods were analyzed for the above constituents. Dietary wheat bran decreased the concentrations of fecal deoxycholic acid, lithocholic acid, 12-ketolithocholic acid, and neutral sterols and the activities of all bacterial enzymes. Oat bran had no effect on secondary bile acids and 7 alpha-dehydroxylase but decreased beta-glucuronidase, nitroreductase, and azoreductase levels. Dietary corn bran increased 7 alpha-dehydroxylase, lithocholic acid, and cholesterol levels and decreased deoxycholic acid coprostanol, cholestenone, nitroreductase, and azoreductase levels. These results show that the modifying effect of dietary fiber on secondary bile acids and bacterial enzymes that may play a role in carcinogenesis depends on the type of fiber consumed.

Adult↗

Comparative tissue tolerance of a new endodontic sealer.

An experimental radiopaque resin root canal sealer was tested for tissue biocompatibility in rat connective tissue. The controls were four widely used sealers: Sealapex, Kerr's sealer, AH-26, and Roth's sealer. Polyethylene tubes were filled with the sealers and allowed to set for 24 hours in 100% humidity. Each sealer was implanted in the connective tissue of Sprague-Dawley rats and removed after 3, 10, 20, 30, and 60 days, fixed, and histologically prepared for light microscope evaluation. At each time period there was practically no difference in the reaction of all the sealers. By 60 days, the total picture was one of well-tolerated biocompatibility.

Animals↗

Control of ventilation in androgenized hypogonadal male rats.

We have previously shown that subcutaneous administration of aspartic acid (a dicarboxylic acidic amino acid) at a dose of 580 mg/kg causes long lasting depression of ventilation in adult intact and postpubertally castrated male rats, but not in intact female rats. The purpose of the present study was to determine if hypogonadism induced by perinatal administration of testosterone propionate (TP) will alter ventilation, oxygen consumption, and the ventilatory response to aspartic acid and to hypercapnia in adult males. TP treatment resulted in adult males who had lower body, prostate, heart, and testes weights than those of control male rats. Ventilation in air and oxygen consumption were comparable between the two groups as was the ventilatory response to aspartic acid. In contrast, TP-treated rats exhibited a significantly decreased ventilatory response to hypercapnia due predominantly to lower tidal volumes compared to control animals. Aspartic acid treatment did not affect oxygen consumption in either group. Thus, TP treatment results in the development of adult male rats who, although hypogonadal, retain a male-like ventilatory response to aspartic acid, but whose response to hypercapnia is more like that of hypogonadal men and rats.

Animals↗

Perinatal estradiol benzoate administration affects control of ventilation in adult male rats.

One injection of estradiol benzoate (EB) (100 micrograms) or vehicle was administered to male rat pups 5 days after birth. Two months later ventilation, ventilatory responses to 7% carbon dioxide, and to 580 mg/kg aspartic acid (an agent used as a marker of sexually dimorphism in the control of ventilation) were evaluated and body weight, testes weight, and nose-anus length were measured in animals in each group. The EB-treated rats had similar tidal volumes, frequency of breathing, and minute ventilation as did control male rats. The ventilatory responses of EB-treated rats to hypercapnia were markedly less than those of control animals. Aspartic acid administration depressed ventilation in control animals, but had no effect on ventilation in EB-treated males. Body and testes weights, as well as nose-anus length, were less in EB-treated compared with control rats. However, when body weight was normalized by nose-anus length and testes weight was normalized by body weight, the values were comparable between the two groups. Thus, perinatal EB treatment of male rat pups results in small, hypogonadal adult animals whose ventilation in response to hypercapnia was diminished and whose response to aspartic acid was female-like relative to those of control rats.

Animals↗

Upregulation of adhesion molecules induced by broncho-vaxom on phagocytic cells.

Whole blood was incubated with the bacterial extract Broncho-Vaxom (OM85) at various concentrations and for different periods of time. Expression of the beta 2-integrins (LFA-1, CD11a/CD18; MAC-1, CD11b/CD18; p150,95, CD11c/CD18) and ICAM-1 (CD54) by monocytes and granulocytes was studied using flow cytometry. OM85 enhanced the expression of MAC-1 and ICAM-1 on monocytes and granulocytes in a dose-dependent manner. Maximal expression was achieved with 1 mg/ml bacterial extract. The effect on MAC-1 expression was not due to the low concentration of endotoxin contaminating the preparation (less than 1 ng/mg) since polymyxin-B did not substantially affect the adhesion molecule upregulation induced by OM85. In addition, OM85 enhanced the expression of p150,95 on monocytes and granulocytes, and also increased expression of LFA-1 on monocytes, but not on granulocytes. While MAC-1 and p150,95 expression reached peak values between 1 and 6 h, levels of ICAM-1 rose constantly for 10 h. We suggest that the clinical interest of OM85 in the management of recurrent infections could be related to be upregulation of adhesion molecules induced by this bacterial extract.

Adjuvants, Immunologic↗

Alloimmunization to platelet antigen HPA-1a (PIA1) is strongly associated with both HLA-DRB3*0101 and HLA-DQB1*0201.

Antibodies to the platelet HPA-1a antigen can elicit in the newborn a condition known as neonatal alloimmune thrombocytopenic purpura (NAITP). Previous studies based on RFLP analysis showed that 100% of HPA-1a-negative women who produced anti-HPA-1a antibodies (responders) were HLA-DRw52a (DRB3*0101). However, this specificity could also be found in some HPA-1a-negative women not producing anti-HPA-1a antibodies (nonresponders). We have analyzed in detail by PCR-SSOP the HLA-DR, -DQ, and -DP loci of 36 responders and 10 nonresponders. We found that while the allele DRB3*0101 was present in the vast majority of responders (91%), there were exceptions. Furthermore, the DQB1*0201 allele was found to be present in almost all responders (94%), but again was also found in nonresponders. The risk of alloimmunization to HPA-1a in an HPA-1b homozygous mother significantly increases with the presence of either allele, the odds ratio being 39.7 for DQB1*0201 and 24.9 for DRB3*0101. Sequencing of exon 2 of these two alleles from responders indicated no sequence difference when compared with the consensus sequences. This indicates that they do not represent variants when compared with the same alleles found in some nonresponders.

Alleles↗

Echocardiographic "smoke" is produced by an interaction of erythrocytes and plasma proteins modulated by shear forces.

OBJECTIVES: This study was designed to determine the blood elements responsible for spontaneous echocardiographic contrast. BACKGROUND: Spontaneous contrast or "smoke" is an echocardiographic image usually found in low flow conditions. Two blood elements, erythrocytes and platelets, have been related to the generation of smoke. METHODS: The echogenicity of porcine blood products was assessed in static and flow conditions and was graded on a digitized videodensity computer program that assigned a score of 0 for black and 100 for white images. Blood elements were circulated from a small tube (4-mm diameter) into a larger cylindric chamber (30-mm diameter) under controlled flow rate conditions. The following blood products were studied: whole blood, platelet-depleted blood, platelet-rich plasma, platelet-poor plasma, erythrocytes suspended in saline solution, adenosine diphosphate (ADP) added to platelet-rich plasma, and saline solution as a control medium. RESULTS: As blood flow was increased in 30 ml/min increments from 0 to 180 ml/min, whole blood echo videodensity (scale 0 to 100) progressively decreased in the larger tube from 38 and 42 to 20, 12, 14, 16 and 14, respectively. When flow increased from 0 to 30 ml/min in the smaller tube, corresponding to a wall shear rate of 0 to 80 s-1, the blood entering the chamber was completely echolucent. The echogenicity of blood products in the larger tube was for static flow (0 ml/min) and high flow (180 ml/min), respectively: platelet-depleted blood = 36 and 14; platelet-rich plasma = 2 and 2; platelet-poor plasma = 0 and 0; erythrocytes in saline solution = 8 and 12; ADP added to platelet-rich plasma = 0 and 15; saline solution = 0 and 0. Because platelets alone were nonechogenic but platelet-depleted blood produced a flow-dependent echogenicity similar to that produced by whole blood, platelets may not be involved in the production of smoke. However, when platelets were aggregated by ADP, they were echogenic but in dense clumps and in a flow-independent pattern not typical of the smokelike images. Erythrocytes suspended in saline solution had an intermediate density image. CONCLUSIONS: Echogenic smoke appears to be due primarily to the interaction of red blood cells and plasma proteins at low flow and low shear rate conditions.

Animals↗

Susceptibility and resistance to autoimmunity following neonatal injection of semi-allogeneic spleen cells in rats.

A model of neonatal allotolerance was developed in rats. Brown-Norway (BN) neonates injected with semi-allogeneic (BN x Lewis) F1 hybrid spleen cells express a long-lasting chimerism and exhibit polyclonal B cell activation demonstrated by hyperimmunoglobulinemia affecting mainly IgE and IgG1, anti-laminin and anti-DNA autoantibodies as well as glomerulonephritis and anti-hapten antibodies. These abnormalities are autoregulated although the chimerism persists. In contrast, Lewis (LEW) neonates injected with semi-allogeneic (BN x LEW) F1 hybrid spleen cells exhibit a very short-lasting chimerism and transient activation of B cells, as reflected by increased allo-class II antigen expression, but do not develop an autoimmune disease. The autoimmune syndrome observed in BN rats is similar to that reported in mice during host-versus-graft reaction. Similarities between the drug-induced models of autoimmunity and allogeneic reactions in BN rats are also striking. The susceptibility of BN rats and the resistance of LEW rats to these autoimmune diseases might respectively reflect the involvement of TH2-like or of TH1-like subsets.

Animals↗

Microleakage--full crowns and the dental pulp.

Recent studies have described microleakage under full crowns cemented with several different cements. This study tested three different types of crown margin preparations--a chamfer, a shoulder, and a shoulder plus a bevel to determine whether or not the margin preparation could affect microleakage. All crowns were cemented with zinc phosphate cement. The crowns were tested for leakage in thermocycled dye. All crowns demonstrated significant leakage following the path of the dentinal tubules into the pulp. This could possibly be one of the causes of pulpal inflammation and even pulpal death under full crowns.

Crowns↗

Procoagulant effect of the OKT3 monoclonal antibody: involvement of tumor necrosis factor.

We recently observed that the prophylactic administration of high doses of OKT3 monoclonal antibody (MoAb) in cadaveric renal transplantation favors the development of thromboses of the grafts' main vessels and of thrombotic microangiopathies. These clinical observations led us to perform sequential determinations of plasma levels of prothrombin fragment 1 and 2 (F 1 + 2) and fibrin degradation products (FDP) after the first injection of 5 or 10 mg OKT3 given as prophylaxis in kidney transplant recipients. The values observed have been compared with those of kidney transplant recipients not treated with OKT3. F 1 + 2 levels peaked four hours after the first injection of 5 mg OKT3 (mean +/- SEM: 4.82 +/- 0.73 vs. 1.75 +/- 0.37 nmol/liter in controls, P < 0.01), indicating activation of the common pathway of the coagulation cascade. FDP levels were already above baseline values at four hours and continued to increase until 24 hours (mean +/- SEM at 24 hr, 4729 +/- 879 vs. 1038 +/- 320 ng/ml in controls, P < 0.05), indicating a fibrinolytic process. The magnitude and the time course of the changes in F 1 + 2 and FDP plasma levels were similar whether the patients received 5 or 10 mg dose of OKT3. The levels of von Willebrand factor (VWF) antigen, a molecule released by activated or damaged endothelial cells, were also significantly increased after injection of OKT3 (mean +/- SEM at 24 hr, 3.67 +/- 0.18 vs. 2.17 +/- 0.11 U/ml in controls, P < 0.05). The procoagulant effects of OKT3 were further investigated in vitro on human umbilical vein endothelial cells (HUVEC).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The long-term effects of prophylactic OKT3 monoclonal antibody in cadaver kidney transplantation--a single-center, prospective, randomized study.

We conducted a randomized, prospective study to determine the long-term effects of prophylactic OKT3 in cadaveric renal transplantation. In the first group of patients (n = 56) OKT3 (5 mg/day) was administered for the first 14 postoperative days in association with azathioprine (AZA) and low-dose steroids, cyclosporine (CsA) being introduced on day 11. The other group of patients (n = 52) received CsA from the first POD, together with AZA and steroids. Both protocols were identical from POD 14 on. The total number of infections was higher in OKT3 patients (124/1455 patient-months [P-M] vs. 68/1320 in CsA patients, P less than 0.001) without impact on patient survival (94.5% in OKT3 vs. 93% in CsA patients). OKT3 patients experienced a lower number of rejection episodes (61 per 1455 P-M of risk exposure vs. 81/1320 in CsA patients, P less than 0.05). In addition, the frequency of corticoresistant rejection episodes was lower in OKT3 patients (9 out of 61 vs. 24 out of 81 in CsA patients, P less than 0.05). This resulted in a trend toward improved overall graft survival (83% vs. 75%, P = 0.12) and in a significant increase in immunological graft survival (92% vs. 79%, P = 0.02) in OKT3 patients at 3 years. Taken together, these data suggest that prophylactic OKT3 therapy might have long-term beneficial effects in cadaveric renal transplantation.

Adult↗

Spleen cell cytokine secretion in Mycobacterium bovis BCG-infected mice.

Three susceptible mouse strains, i.e., BALB/c (H-2d), C57BL/6 (H-2b), and major histocompatibility complex-congenic BALB.B10 (H-2b), were infected intravenously with 4 x 10(6) CFU of live Mycobacterium bovis BCG and analyzed 4 weeks later for in vitro spleen cell cytokine secretion in response to purified protein derivative (PPD), BCG culture filtrate (CF), BCG cellular extract, total BCG, the purified extracellular 30-32-kDa antigen (the fibronectin-binding antigen 85), or the intracellular 65-kDa heat shock protein. C57BL/6 and BALB.B10 mice produced 5- to 10-fold more gamma interferon and interleukin-2 (IL-2) when stimulated with CF, PPD, and antigen 85 than BALB/c mice did. When stimulated with BCG extract and whole BCG, gamma interferon and IL-2 levels were generally lower and comparable in the three strains. IL-4 was detected in spleen cell culture supernatants from infected BALB/c mice but not from C57BL/6 or BALB.B10 mice. IL-5 could not be detected. C57BL/6 and BALB.B10 spleen cells also produced more tumor necrosis factor alpha and IL-6 after stimulation with PPD and CF than BALB/c cells did. Finally, BCG vaccination generated efficient protective immunity in C57BL/6 and BALB.B10 mice but not in BALB/c mice. These data suggest that secreted mycobacterial CF antigens selectively induce a strong TH1 response in BCG-infected C57BL/6 and BALB.B10 mice, whereas in BALB/c mice this response is partly counterbalanced by TH2 cells.

Animals↗

Effect of aspartic acid on control of ventilation in androgenized and ovariectomized female rats.

Previously we observed that acute subcutaneous administration of aspartic acid (580 mg/kg) depressed ventilation in awake male, but not female, rats, suggesting that this agent may be used as a marker for sexual dimorphism in the control of ventilation. Moreover, males castrated postpubertally showed a response similar to that of intact male rats. Thus the hormonal milieu of male rats appear not to be necessary to elicit the masculine type of ventilatory response to aspartic acid. The purpose of this study was 1) to determine whether adult female rats androgenized by the administration of testosterone propionate (TP) 1 day after birth would alter their ventilation in response to aspartic acid to be more malelike and 2) to compare these results with those of intact (I) and ovariectomized (O) female rats. Minute ventilation and O2 consumption in air and in response to aspartic acid administration were evaluated in awake animals in all three groups. Furthermore the minute ventilation of all rats to a hypercapnic challenge was also evaluated. Ovariectomy resulted in rats increased body weights but decreased weight-corrected ventilation and O2 consumption compared with TP-treated and I animals. Minute ventilation after hypercapnic challenge in the three groups was similar. TP-treated rats responded to aspartic acid administration with a marked depression of ventilation similar to that previously noted in males, whereas neither I nor O rats showed such a response. The depression of ventilation in the TP-treated group in response to aspartic acid was not a consequence of a depression of O2 consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗