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S C Jordan

Publications and source records attributed to S C Jordan.

At least 73 records · Page 4Linked to original sources
PubMed1993

Tumor necrosis factor alpha modulates parathyroid hormone action in UMR-106-01 osteoblastic cells.

Tumor necrosis factor (TNF-alpha) has been shown to play an important role in local control of bone remodeling. The interaction of TNF-alpha and PTH was evaluated in UMR-106-01 cells, a phenotypic osteoblastic osteosarcoma cell line. We examined the influence of TNF-alpha on the two signal transduction systems triggered by PTH in UMR-106-01 cells, adenylate cyclase and free cytosolic calcium ([Ca2+]i). cAMP generation was inhibited in TNF-alpha-pretreated cells by 69, 61, 34, and 21% at PTH concentrations of 0.1, 1, 10, and 100 nM, respectively. Inhibition was seen at TNF-alpha doses of 100-1500 units/ml after a minimum incubation time of 12 h. TNF-alpha inhibition of the PTH-stimulated increase in [Ca2+]i was even more pronounced: treated cells showed no change in baseline [Ca2+]i after stimulation with 40 nM PTH. Treatment with TNF-alpha was also found to inhibit both arms of the PTH response in the nontransformed osteoblastic cell line, MC3T3-E1. TNF-alpha treatment did not alter cAMP generation in response to PGE2. TNF-alpha inhibition of the PTH-stimulated cAMP response was reversed completely by addition of cholera toxin (5 micrograms/ml) and partially by forskolin (10 microM) but not pertussis toxin (100 and 500 ng/ml). Scatchard analysis using PTHrP revealed that TNF-alpha treatment reduced the number of receptors but had no effect on KD. These findings suggest that TNF-alpha inhibits the osteoblastic response to PTH at least in part because of a reduction in receptor number. Further investigation is indicated to provide insight into the interaction of calciotropic hormones and cytokines in vivo.

Adenylate Cyclase Toxin↗
PubMed1993

Modulation of MHC expression on human endothelial cells by sera from patients with systemic lupus erythematosus.

Major histocompatibility complex (MHC) antigen expression on cells is a prerequisite for immune interaction with activated T-cells. This study examined the ability of sera from patients with systemic lupus erythematosus (SLE) to modulate MHC expression on vascular endothelial cells. SLE sera were able to selectively upregulate MHC class I antigen expression on cultured human umbilical venous endothelial (HUVE) cells, without concomitant induction of MHC class II antigen. The stimulation index (SI) for MHC class I expression produced by SLE sera (1.21 +/- 0.23) was significantly higher than those for normal controls (1.01 +/- 0.10) (P < 0.0001) and non-SLE patients (1.12 +/- 0.14) (P < 0.05). Additionally, active SLE patients had higher mean SI than inactive patients (P < 0.001). Preincubation of SLE sera with Protein A-Sepharose beads conjugated with antibodies against tumor necrosis factor-alpha and interferon-alpha was able to significantly reduce their ability to upregulate class I MHC expression by HUVE cells, indicating that these cytokines were responsible for the modulatory effect. This could be an important mechanism for the immune-mediated vascular injury seen in SLE.

Adolescent↗
PubMed1993

Immunocytologic analysis of cells obtained from bronchoalveolar lavage in a model of rat lung allograft rejection.

Left lung transplantation (n = 30) between BN rat (RT1n) and LEW rat (RT1(1)) was performed to examine serial changes in the inflammatory cell profile and T-cell subsets occurring in bronchoalveolar lavage (BAL) obtained after transplantation. Transplanted animals were sacrificed on Days 1 to 7 post-transplantation. Previous studies show that lung allografts between these rat strains were strongly rejected within 7 days. The serial change in the cell profile of BAL showed a marked initial predominance of polymorphonuclear leukocytes, a decrease in macrophages, and a temporary increase in number of eosinophils on Day 2 post-transplantation. A gradual increase in lymphocytes coincident with progression of rejection was also noted. Immunocytologic studies using monoclonal antibodies specific for rat T-cell subsets and interleukin-2 receptor (IL-2R) showed significant increase in pan-T-cells on Days 3, 4, and 5 and T-suppressor/cytotoxic (CD8 positive) fraction on Days 4 and 5, whereas the T-helper (CD4 positive) fraction peaked on Day 2. The frequency of T-cells expressing IL-2R (55 kDa), indicating activated T-cells, significantly increased as early as Day 2 and maintained its high value thereafter. mRNA levels for IL-2R were detectable in the allografts on Day 2 and peaked on Day 5 post-transplantation. The value of CD4/CD8 T-cell ratios rose initially and then dropped below 1.0 on Days 4 and 5. These values differed markedly from those of syngeneic transplants (Lew-->Lew) examined on Day 5 post-transplantation. First, no significant changes in BAL cytology were seen when syngeneic transplants were compared with normal (Lew) lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The participation of tumor necrosis factor in the pathogenesis of lung allograft rejection in the rat.

Tumor necrosis factor alpha and beta are polypeptide cytokines with a wide range of metabolic, immunologic, and inflammatory activities. TNF is known to participate in immune mediated injury of native lungs, but a role for TNF in mediating lung allograft rejection (AR) has not been established. In experiments reported here, we assessed the role of TNF in mediating lung AR in a rat model of lung transplantation (BN-->Lew) (RT1n-->RT1l). This model shows florid AR with all grafts completely destroyed by day 6 posttransplant. Graft pathology is characterized by massive lymphocytic infiltrates and hemorrhagic necrosis. Initially, 5 lung allograft recipients in each group were sacrificed on days 1 to 6 posttransplant. Allografts were removed, mRNA isolated, and Northern blotting or RT-PCR performed with blots probed with cDNAs or oligos specific for rat TNF-alpha cyclophylin and gamma-actin. Data were compared with syngeneic transplants (Lew-->Lew) and with normal controls. In addition, frozen lung allograft tissue was examined by indirect immunofluorescence, using antibodies specific for TNF. TNF-alpha mRNA levels were detectable on day 2 posttransplant, and peaked on days 6-7 posttransplant. IF studies showed TNF protein expression in mononuclear cells of rejecting allografts on day 3, peaking on day 6. Both TNF-alpha mRNA and protein levels correlated with maximal AR and hemorrhagic necrosis of grafts. Minimal TNF-alpha mRNA or protein was detected in syngeneic grafts or in contralateral native lungs. We then examined the ability of a rabbit polyclonal anti-TNF-alpha (7000 U/day) and anti-TNF-beta (5000 U/day) with 30% crossreactivity with rat TNF to modify the AR response. For each group, 4-5 left lung transplants were performed as described, and animals treated with anti-TNF-alpha, anti-TNF-beta, (anti-TNF-alpha+anti-TNF-beta) or with preimmune rabbit sera. All animals were sacrificed on day 6 posttransplant. Several pathological categories of inflammation were examined and scored (0-4), with a score of 0 = 0% involvement; 1 = 1-25% involvement; 2 = 26-50% involvement; 3 = 51-75% involvement; and 4 = 76-100% involvement. The mean and SD scores were obtained for all animals in the treatment categories mentioned above, and compared with preimmune-treated controls. Briefly, no differences in perivascular, peribronchial, or peribronchiolar cell infiltrates or edema were seen in treatment groups compared with controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Radiofrequency-assisted balloon dilatation in patients with pulmonary valve atresia and an intact ventricular septum.

OBJECTIVE: To investigate the efficacy and safety of transcatheter radiofrequency-assisted valve dilatation for infants with pulmonary valve atresia and intact ventricular septum as an alternative to the use of laser heated wires. DESIGN: Prospective clinical study. SETTING: Three paediatric cardiology centres. PATIENTS: Four children (aged 5-101 days, weight 2.8 kg) with pulmonary valve atresia and intact ventricular septum underwent percutaneous radiofrequency-assisted valve dilatation. METHODS: After delineating the atretic valve by angiography, 0.020 inch or 0.018 inch radiofrequency wires were used to perforate the atretic valve. The valve was then dilated with conventional balloon dilatation catheters up to the valve annulus diameter. RESULTS: In all four cases the radiofrequency wire perforated the atretic pulmonary valve and balloon dilatation was successful. In one patient the radiofrequency wire also passed through the anterior wall of the pulmonary artery causing tamponade which required surgical repair shortly afterwards. This patient died from sepsis six days later. One patient died three weeks after the procedure from septicaemia and a paradoxical coronary embolus. Two patients were discharged after 4 and 14 days respectively. CONCLUSIONS: Radiofrequency-assisted valve dilatation is a promising alternative to the recently developed laser wire technique. The major advantages are a reduction in cost and improved safety for the staff performing the procedure.

Balloon Occlusion↗
PubMed1993

Medium-term clinical results after the Senning procedure with haemodynamic and angiographic evaluation of the venous pathways.

OBJECTIVE: To assess the clinical condition of patients and the adequacy of their newly constructed venous pathways after the Senning operation for simple transposition of the great arteries. PATIENTS AND DESIGN: All 34 patients who had the Senning operation between March 1983 and December 1986 were reviewed. Survivors had detailed cardiac catheterisation studies one to two years later and clinical evaluation two to six years after surgery. RESULTS: There were two operative deaths (6%), one sudden late death (after two years), and 31 survivors (91%). No clinical evidence of obstructed venous pathways was found and there was no need for reoperation for any reason. The average mean (SD) pressure gradient at the junction of the superior vena cava and systemic venous atrium was 2.0 (1.7) mm Hg, although two patients had gradients of 7 mm Hg. The average gradient was 0.7 (1) mm Hg in the inferior vena caval pathway, and 1.4 (1.1) mm Hg between the mean pulmonary arterial wedge and pulmonary venous atrial pressures. Only the two patients with gradients of 7 mm Hg at the junction of the superior vena cava and the systemic venous atrium had considerable narrowing of the pathway and retrograde flow in the azygos vein to below the diaphragm. CONCLUSION: A small series of patients were comprehensively studied after the Senning operation for simple transposition of the great arteries. Scrupulous technique in the construction of the venous pathways has had excellent results with no need for reoperation for obstruction in either the systemic or pulmonary pathways. Clinical observation alone may fail to identify patients with venous pathway obstruction, therefore careful assessment is required, even in patients who are physically normal.

Angiography↗
PubMed1993

Balloon dilatation (valvoplasty) as first line treatment for severe stenosis of the aortic valve in early infancy: medium term results and determinants of survival.

OBJECTIVE: To assess the results of balloon dilatation of the aortic valve as first line treatment for infants presenting in the first two months of life with cardiac failure caused by severe aortic stenosis. DESIGN: A prospective study of all such infants presenting to a single centre over a three year period. PATIENTS: Of 14 consecutive infants aged < 2 months presenting with heart failure due to severe stenosis of the aortic valve, 12 underwent balloon dilatation of the valve. Two infants with hypoplastic left heart syndrome were excluded. Six patients had other significant cardiac malformations, nine had endocardial fibroelastosis. Four infants were moribund at presentation. INTERVENTIONS: Balloon dilatation was performed through the femoral artery under general anaesthetic, with heparin and antibiotic prophylaxis. Maximum inflated balloon size was selected as equal to or slightly less than the diameter of the aortic valve measured echocardiographically. In two infants balloon dilatation of coexistent severe coarctation was performed at the same time. RESULTS: Dilatation was achieved in all cases. Early survival rate (up to one month) was 75%; 50% survive up to three years. The two deaths occurring < 24 hours after dilatation probably related to the infants' poor condition at presentation and the presence of significant left ventricular hypoplasia. The other early death was due to severe mitral regurgitation from papillary muscle dysfunction. All later deaths were related to associated malformations. The difference in left ventricular size (diameter and length) measured echocardiographically at presentation between survivors and those that died is significant (p < or = 0.002). 83% of deaths occurred in infants with associated malformations. Cusp perforation occurred in one infant, which may have contributed to this patient's death. Left ventricular perforation and cardiac tamponade were treated successfully by prompt pericardiocentesis in another. CONCLUSIONS: Balloon dilatation of the aortic valve is an acceptable first line treatment for neonates with severe symptomatic stenosis of the aortic valve. Outcome depends principally on left ventricular size and on the presence, severity, and timing of treatment of associated malformations. Severe endocardial fibroelastosis was not a risk factor for early death but may have implications for long term survival. The survival rate for this high risk group might be improved by a stratified approach where patients with adequate left ventricular size have balloon dilatation whereas those with severe ventricular hypoplasia are managed like patients with the hypoplastic left heart syndrome.

Aortic Valve↗
PubMed1993

Immunosuppression in organ transplantation.

Recent advances in the development of immunosuppressive agents, including newer immunophylin drugs such as FK-506 and lymphocyte DNA synthesis inhibitors such as RS-61443, have allowed rapid progress to be achieved in the prevention and treatment of allograft rejection. Soon, these drugs will join cyclosporine and OKT3 as significant advancements in our battle against allograft loss and dysfunction caused by rejection. Newer developments in immunosuppressive therapy depend on our ability to understand how the immune system works in mediating allograft destructive events. Therefore it is critical that our basic understanding of immunologic mechanisms be incorporated into the development and use of current and future immunosuppressive agents.

Child↗
PubMed1992

Potentiation of lipopolysaccharide-induced tumor necrosis factor-alpha expression by 1,25-dihydroxyvitamin D3.

The immunomodulatory hormone 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to suppress T-cell proliferation and interleukin-2 synthesis as well as B-cell immunoglobulin synthesis, while stimulating many macrophage functions. We have previously shown increased synthesis of interleukin-1 beta in lipopolysaccharide (LPS)-stimulated U937 cells after pretreatment with 10 nmol/L 1,25-(OH)2D3. We now show that 1,25-(OH)2D3 also primes the increase in U937 cell tumor necrosis factor (TNF)-alpha-accumulated mRNA after activation with LPS; 50% effective concentration (EC50) for the LPS-induced expression of TNF-alpha mRNA was decreased by two orders of magnitude after incubation with 10 nmol/L 1,25-(OH)2D3. Pretreatment of U937 cells with 10 nmol/L 1,25-(OH)2D3 also increased subsequent LPS-induced TNF-alpha mRNA expression by twofold and cell-associated TNF protein levels by more than ninefold. This potentiation was steroid-specific for 1,25-(OH)2D3 because dexamethasone inhibited TNF-alpha mRNA. The potentiation required prior exposure to 1,25-(OH)2D3 for more than 6 hours and was clearly seen after 12 hours. The finding that the sensitivity of the U937 cell monokine response to LPS was dramatically increased by 1,25-(OH)2D3 and the delayed effect on the LPS-stimulated TNF-alpha gene transcript levels indicated that 1,25-(OH)2D3 may be altering the expression of a protein(s) in the U937 cell LPS-signal transduction pathway. In fact, 1,25-(OH)2D3 induced expression of the mRNA for CD14, the high affinity, cell-surface glycoprotein receptor for LPS, which could account for the enhancement of LPS-stimulated monokine gene expression by 1,25-(OH)2D3. Thus, local monokine gene expression may be regulated by both the amount and the temporal entry of the vitamin D hormone and activator(s) into the inflammatory microenvironment.

Blotting, Northern↗
PubMed1992

Treatment of antineutrophil cytoplasmic autoantibody-positive systemic vasculitis and glomerulonephritis with pooled intravenous gammaglobulin.

Antineutrophil cytoplasmic autoantibody (ANCA) is considered a serological marker for disease activity in patients with ANCA(+) systemic vasculitis. Recently, ANCA has been implicated as a pathogenic antibody that may be associated with neutrophil degranulation and release of lytic enzymes. Since intravenous gammaglobulin (IVIG) is known to contain antiidiotypic antibodies to ANCA, which could decrease the activity of the later, we chose to treat two patients with symptomatic ANCA(+) systemic vasculitis and glomerulonephritis with high-dose IVIG. The first patient, a 66-year-old man, developed rapidly progressive renal failure despite treatment with intravenous (IV) cyclophosphamide. The second patient, a 14-year-old boy, had relapsed 3 months after cessation of treatment with prednisone and cyclophosphamide. Both patients improved dramatically after treatment with IVIG, with the former recovering renal function within 11 days of therapy. In both patients, a concomitant reduction in serum ANCA titers was also observed. The second patient is currently in a sustained remission 14 months after his last IVIG dose on no other medication. These cases provide clinical evidence that IVIG has therapeutic benefit in modifying the immune-mediated injury associated with ANCA(+) systemic vasculitis and glomerulonephritis. In addition, IVIG may provide an additional safe therapeutic option to clinicians treating patient's with ANCA(+) vasculitis and glomerulonephritis who are not responsive to or are experiencing toxicity from conventional therapy.

Adolescent↗
PubMed1991

Vascular rejection and graft eosinophilia in rat lung allografts.

Allogeneic lung transplantation was performed using a rat model in order to assess the pathologic changes that developed during the process of rejection. The left lungs of 38 BN rats (RT-1n) were orthotopically transplanted into LEW rats (RT-1). The allografts developed the well-known changes of perivascular, peribronchial, and interstitial lymphocytic infiltrates resulting in necrosis of the pulmonary parenchyma at 7-8 days after transplantation. In addition, we document two findings that have not been reported previously in lung transplantation: vasculitis and eosinophilic infiltrates. Vasculitis with swelling and vacuolization of the endothelial cells was observed in transplants as early as 3 days following transplantation. Vasculitis with fibrinoid necrosis of the vessel wall was prominent at 7-8 days after grafting. The allografts also exhibited eosinophilia at 2 to 4 days following transplantation. The density of eosinophils in the inflammatory infiltrate reached a peak of 20% on Day 3 post-transplantation. These findings suggest an important role of humoral immunity and a possible involvement of eosinophils in lung allograft rejection.

Animals↗
PubMed1991

Stimulus-specific 1,25(OH)2D3 modulation of TNF and IL-1-beta gene expression in human peripheral blood mononuclear cells and monocytoid cell lines.

It is known that 1,25(OH)2D3 inhibits IL-2, IFN-gamma, and GM-CSF mRNA accumulation in activated T cells. While 1,25(OH)2D3 enhances macrophage competence, its effect on cytokine gene expression in monocytes is less well defined. Using Northern blot analysis, we examined the effect of 1,25(OH)2D3 pretreatment on IL-1 beta and TNF gene expression in LPS- and PHA-stimulated human PBMNC and several human myeloid cell lines (U937 and THP1). In PBMNC, preincubation had no effect on the steady-state level of LPS-induced TNF or IL-1 beta mRNA. When PHA was used to stimulate pretreated PBMNC, a 60-80% inhibition of TNF mRNA levels was observed. There was no effect on IL-1 beta mRNA. In U937 cells, 1,25(OH)2D3 preincubation resulted in a 4-fold increase in the level of TNF and IL-1 beta mRNA levels. Pretreatment had no effect on TNF or IL-1 beta gene expression in THP1 cells. The observation that PHA-induced TNF gene expression is modulated by 1,25(OH)2D3 is novel. Possible mechanisms by which 1,25(OH)2D3 preincubation may influence mitogen-specific inducible cytokine gene expression in different cell types are discussed.

Blotting, Northern↗
PubMed1991

Cell-mediated immunity in patients on hemodialysis: relationship with hepatitis B carrier status.

We compared cell-mediated immune responses in two groups of patients on hemodialysis. One group of patients were chronic carriers of hepatitis B virus (HBV), and the patients of the other group were HBV antigen negative. Our results show that despite the presence of normal numbers of T cells and an increased CD4/CD8 ratio in both groups of patients compared to healthy controls (p less than 0.0001), only the group of patients who were chronic HBV carriers showed depressed lymphoproliferative responses to phytohemagglutinin (p less than 0.001) and concanavalin A (p less than 0.0001). In contrast, a control group of healthy adult HBV carriers showed normal T cell subsets and lymphoproliferative responses to mitogens, indicating that HBV infection per se did not result in depressed lymphoproliferative responses. These results further substantiate the notion that depressed cell-mediated immunity in chronic renal failure is an important factor in predisposing patients to HBV infection with subsequent development of the chronic carrier state.

Adult↗
PubMed1991

The human myelomonocytic cell line U-937 as a model for studying alterations in steroid-induced monokine gene expression: marked enhancement of lipopolysaccharide-stimulated interleukin-1 beta messenger RNA levels by 1,25-dihydroxyvitamin D3.

The active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], is a potent regulator of human monocyte/macrophage function in vitro. To establish a model for 1,25-(OH)2D3 regulation of human monocyte monokine synthesis, three human cell lines (U-937, THP-1, and HL-60) were examined for: 1) the presence of functional 1,25-(OH)2D3 receptors; 2) the accumulation of interleukin-1 beta (IL-1 beta) mRNA and IL-1 beta protein in response to lipopolysaccharide (LPS); and 3) the regulation of this response by 1,25-(OH)2D3. All three cell lines expressed vitamin D receptor and had increased levels of IL-1 beta mRNA in response to LPS. Preincubation of cells with 1,25-(OH)2D3 augmented IL-1 beta mRNA levels only in U-937 and HL-60 cells. From these data, and taking into consideration their state of differentiation and relative ease of culture, U-937 was chosen over HL-60 and THP-1 as the cell line we further characterized. In U-937 cells, optimum time and dose of pretreatment with 1,25-(OH)2D3 were determined to be 12-24 h at a receptor saturating concentration of 1,25-(OH)2D3 (10 nM). Preincubation of cells with 1,25-(OH)2D3 had no effect on the time course of IL-1 beta mRNA appearance in response to LPS. However, exposure of U-937 cells to 1,25-(OH)2D3 increased by 200% the level of IL-1 beta mRNA detected and decreased by three orders of magnitude the concentration of LPS required to achieve steady state mRNA levels equivalent to those observed in U-937 cells not preincubated with the hormone.2+o

Calcitriol↗
PubMed1991

Inhibition of protein-kinase C in peripheral blood mononuclear cells of patients with systemic lupus erythematosus: effect on spontaneous immunoglobulin production.

Systemic Lupus Erythematosus (SLE) is a multisystem disease characterized by an increase in the spontaneous secretion of immunoglobulin (Ig) molecules, many of which are autoreactive. We have previously shown (Biochem & Biophys. Res. Comm. (1989) 161: 1319-1326) that normal human peripheral blood mononuclear cells (PBMCs) can be stimulated to secrete large quantities of Ig upon incubation with the protein kinase-C activator 1 oleoyl-2-acetyglycerol (OAG). Specific blockage of protein kinase C with the isoquinoline sulfonyl piperazine compound (H-7) inhibited the OAG-induced Ig production. In experiments reported here, PBMC of 5 patients with active SLE produced high levels of IgG spontaneously in culture. PBMC of 6 inactive SLE patients and 7 normal control subjects produced comparable low levels of IgG spontaneously. Pokeweed mitogen (PWM) stimulation of PBMC in inactive SLE and control groups, but not active SLE patients produced markedly enhanced IgG production. The lack of response to PWM stimulation in active SLE patients is likely due to inherent maximal stimulation of active SLE B-cells. In addition, we examined the ability of H-7 to inhibit both mitogen-stimulated (normal and inactive SLE) and spontaneous (active SLE) Ig production. In other experiments, we also examined the ability of the isoquinoline sulfonamide (HA-1004), a potent inhibitor of cAMP-dependent protein kinase to regulate mitogen stimulated and spontaneous Ig production in the patient groups indicated above. H-7 significantly inhibited PWM stimulated Ig production in normal (P less than 0.0001) and inactive SLE patients, (P less than 0.040) suppressing PWM stimulated levels to spontaneous levels.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗