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Biomedical subjects

J D Sipe

Publications and source records attributed to J D Sipe.

At least 91 records · Page 5Linked to original sources
PubMed1985

Effect of colchicine on experimental amyloidosis in two CBA/J mouse models. Chronic inflammatory stimulation and administration of amyloid-enhancing factor during acute inflammation.

To investigate the mechanism of action of colchicine in blocking amyloid deposition, two model systems of amyloidosis in CBA/J mice were studied. In experimental chronic inflammation, daily injection of silver nitrate (AgNO3) resulted in the deposition of 667 +/- 68 ng of amyloid A protein (AA)/mg of spleen after 25 days. Treatment with 10 micrograms of colchicine daily decreased AgNO3-induced AA deposition to 12 +/- 1 ng of AA/mg of spleen (p less than 0.001). Colchicine diminished the acute phase serum amyloid A protein (SAA) response after 24 hours. Over a 25-day period, SAA concentrations declined and approached baseline both in colchicine-treated and (unexpectedly) in control mice. This suggested that suppression of SAA levels was not the primary event inhibiting amyloid deposition. In a model of accelerated amyloid deposition, injection of preformed amyloid-enhancing factor along with AgNO3 induced the deposition of 974 +/- 46 ng of AA/mg of spleen 48 hours later. Colchicine only partially decreased amyloid-enhancing factor-induced amyloid deposition to 578 +/- 91 ng of AA/mg of spleen, while blunting the acute phase SAA response. These results suggest that colchicine inhibits amyloidosis in the predeposition phase, possibly by blocking formation of amyloid-enhancing factor.

Amyloid↗
PubMed1985

Prostaglandin E1 inhibition of experimental amyloidosis in CBA/J mice.

The antiinflammatory activity of systemically administered prostaglandin E1 (PGE1) was studied in experimental CBA/J mouse amyloidosis induced by chronic stimulation with silver nitrate. PGE1 lowered splenic deposition of amyloid A protein (AA) (p = 0.035). Serum amyloid A protein (SAA) levels were not suppressed by PGE1 in the acute phase, while decreased SAA levels appeared to be an integral part of the chronic inflammatory phase, with or without PGE1 treatment. Accelerated amyloid deposition induced by amyloid-enhancing factor (AEF) was not blocked by PGE1. This suggests that PGE1 inhibits amyloidosis in the predeposition phase, possibly by preventing formation of AEF or other deposition factors.

Alprostadil↗
PubMed1984

Measurement of murine serum amyloid P component by rate nephelometry.

Murine serum amyloid P component (SAP) is an acute-phase protein that is increased 2-10-fold in concentration following appropriate inflammatory or infectious stimuli. Previous studies of the acute-phase SAP response have employed quantitative immunoelectrophoresis or radioimmunoassay to measure SAP concentration. A rate nephelometric procedure has been developed which measures SAP concentration rapidly and with equivalent or greater precision than the previously applied techniques. This simple method will facilitate experimental and clinical studies of the acute-phase response.

Acute-Phase Proteins↗
PubMed1984

Quantitation of serum suppressor factor, related to the erythrocyte receptor of human peripheral blood T lymphocytes as measured by radioimmunoassay.

A solid phase radioimmunoassay for a serum suppressor factor has been developed. The factor was previously purified from malignant ascites fluids and shown to be related to the sheep erythrocyte receptor of human peripheral blood T lymphocytes. This humoral suppressor factor has been termed suppressive E-receptor factor. Using this assay, it was demonstrated that both ascites fluids and sera derived from patients with solid tumors contain elevated levels of this factor compared to similar specimens from patients with a variety of nonmalignant diseases. The concentration of this SER factor does not correlate with serum immunoglobulin G levels but it does correlate with the ability of sera from individual patients to inhibit phytohemagglutinin-induced DNA synthesis by normal human peripheral blood T lymphocytes. Kinetically, this suppressive E-receptor factor directly competes with monoclonal antibody directed to the sheep erythrocyte receptor of human peripheral T lymphocytes and exhibits noncompetitive-type inhibition of DNA synthesis induced by phytohemagglutinin.

Antibodies, Monoclonal↗
PubMed1984

Acute-phase proteins or tumour markers: the role of SAA, SAP, CRP and CEA as indicators of metastasis in a broad spectrum of neoplastic diseases.

Two hundred and seventy-seven patients with a broad spectrum of neoplastic diseases, including 10 classes of solid tumours and three classes of haematologic malignancies, were retrospectively surveyed, and from the same sample of plasma or serum their concentrations of serum amyloid A (SAA), serum amyloid P component (SAP), C-reactive protein (CRP), and carcinoembryonic antigen (CEA) were measured. SAA levels varied from 105 ng/ml to 105,000 ng/ml, and mean SAA levels were higher in patients with metastatic tumours than in those with limited disease (P less than 0.001). Similarly, CRP levels varied from less than 8 micrograms/ml to 328 micrograms/ml and were significantly higher in the metastatic disease category. In contrast, SAP levels varied from 32 micrograms/ml to 120 micrograms/ml and showed no difference in patients with limited or metastatic disease, although an overall slight elevation was present. CEA levels were available in 150 patients and were significantly higher in patients with advanced lung or breast cancer than in patients with limited disease. The correlation between mean SAA and CRP levels was significant (r = 0.74, P less than 0.001), suggesting that SAA originates as an acute-phase protein rather than as a tumour cell product. However, the consistent elevation of SAA in all tumour types and the more marked elevation in metastatic disease may make its measurement useful in malignancy.

Acute Disease↗
PubMed1984

Serum amyloid A protein concentration in progressive systemic sclerosis (scleroderma).

Serum amyloid A protein (SAA) concentrations were determined in 62 patients with progressive systemic sclerosis (PSS). Forty-seven patients had normal or slightly elevated SAA levels (less than 1000 ng/ml = micrograms/l), while 15 patients had moderately to markedly elevated SAA levels, similar to those observed in active rheumatoid arthritis (RA) (greater than or equal to 1000 ng/ml = micrograms/l). Five patients with PSS had SAA levels corresponding to those observed in amyloidosis secondary to RA. High SAA was associated with more severe skin thickening and diminished cumulative survival at five years. The rarity of amyloidosis secondary to PSS is unlikely to be related to an intrinsic defect in SAA production.

Amyloid↗
PubMed1984

Cloning of human prealbumin complementary DNA. Localization of the gene to chromosome 18 and detection of a variant prealbumin allele in a family with familial amyloid polyneuropathy.

Prealbumin, a 55,000 Mr protein, is a normal constituent of human serum. In patients with familial amyloid polyneuropathy (FAP), an autosomal dominant disease, variant prealbumin molecules are found in association with systemic amyloid deposits. One variant prealbumin has a methionine for valine substitution at amino acid 30 and has been implicated in the pathogenesis of type 1 FAP. A prealbumin-specific complementary DNA clone has been isolated from an adult human liver library and used in Southern blot hybridization experiments to identify a unique NsiI restriction endonuclease site in the variant allele carried by type 1 FAP patients with the methionine for valine substitution. The complementary DNA clone has been used to analyse a panel of human-mouse and human--hamster somatic cell hybrid DNAs and localize the prealbumin gene to chromosome 18.

Alleles↗
PubMed1984

Colchicine in acute inflammation: stimulation of production of interleukin-1 and modulation of the acute phase serum amyloid A protein response.

The effects of colchicine on the acute phase serum amyloid A (SAA) response were studied in CBA/J mice to determine whether these effects are mediated via inhibition of interleukin-1 (IL-1) production. Prolonged pretreatment (72 h) with colchicine blunted the SAA response to stimulation with silver nitrate (AgNO3), while brief pretreatment (12 h) unexpected augmented SAA production. In a macrophage model, colchicine stimulated baseline production of IL-1 (SAA inducer and lymphocyte activating factor activities) and augmented lipopolysaccharide (LPS) induced IL-1 production. This indicates that colchicine does not inhibit amyloidosis via direct effects on early inducers of the acute phase SAA response.

Amyloid↗
PubMed1983

Different regulatory mechanisms for serum amyloid A and serum amyloid P synthesis by cultured mouse hepatocytes.

Regulation of the in vitro synthesis of the serum amyloid proteins A and P has been studied with hepatocyte cultures from CBA/J and C3H/HeJ mice. Liver cells were isolated by the collagenase perfusion technique and established for 48 h in the presence of fetal calf serum. Viable cells could then be maintained in the absence of serum for at least 72 h and in the presence of serum for up to 2 weeks. Serum amyloid A synthesis differed from serum amyloid P synthesis in three significant ways. 1) Serum amyloid A production was stimulated in the presence of fetal calf serum, whereas serum amyloid P was not; 2) serum amyloid A synthesis was increased 200% by monokine-rich macrophage supernatants while serum amyloid P was increased only 10 to 20%; 3) serum amyloid A synthesis was strikingly resistant to cycloheximide inhibition as compared with serum amyloid P and other liver proteins. It is concluded that the in vivo asynchrony of the acute phase serum amyloid A and serum amyloid P responses results at least in part from differences in regulatory mechanisms for their synthesis by hepatocytes.

Amyloid↗
PubMed1982

The role of interleukin 1 in acute phase serum amyloid A (SAA) and serum amyloid P (SAP) biosynthesis.

The acute phase SAA and SAP profiles have been compared for localized and endotoxin induced inflammation in LPS responder and nonresponder strains of mice. The SAP profile can reflect a delay with respect to the start of the increase. Its maximum is on the order of ten times the nonacute phase concentration and elevated concentrations are sustained 24 to 48 hours after SAA concentration is rapidly decreasing to normal. The role of Interleukin 1, known to have an essential role in SAA production, was investigated for SAP production. Purified mouse IL 1 and rabbit IL 1 produced a minimal elevation of SAP concentration above normal values, especially when compared with their effects on SAA concentration. BCG infection was shown to synergistically augment SAA induction by LPS and was shown to enhance IL 1 production by macrophages in response to LPS. Unlike SAA synthesis, BCG-preinfection fails to synergistically augment the LPS-induced SAP response. BCG infection alone produced highly elevated and sustained increases in SAP concentration, whereas, the effect on SAA concentration was minimal. Macrophages appear to play an important role in SAP acute phase elevation, but the mechanism in different from that of SAA elevation.

Acute Disease↗
PubMed1980

Monokine-induced synthesis of serum amyloid A protein by hepatocytes.

Infection or inflammation triggers the rapid appearance in the blood of a group of proteins known as acute phase reactants. Serum amyloid A protein (SAA) is an acute phase protein which is believed to be the precursor for the secondary amyloid fibril protein, known previously as amyloid of unknown origin, and now as amyloid A protein (AA). The site of synthesis of SAA has been controversial, with previous evidence suggesting that AA related proteins arise in liver, connective tissues, polymorphonuclear neutrophil leukocytes and spleen. However, in none of these systems could SAA synthesis be induced in vitro and the evidence rested on studies of tissues or cells arising from pre-stimulated animals. Our aim in the present studies was to prove that the liver is capable of SAA production and to identify the specific cell responsible for synthesis. The experiments demonstrate that SAA is synthesized in the liver by hepatocytes. In addition, colchicine, currently used for the treatment of amyloidosis, blocks the secretion of SAA from the hepatocyte, as has been shown for another acute phase reactan, C-reactive protein.

Amyloid↗
PubMed1980

BCG-induced enhancement of endotoxin sensitivity in C3H/HeJ mice. I. In vivo studies.

C3H/HeJ mice exhibit a marked insensitivity to bacterial lipopolysaccharide (LPS) in vivo. Pretreatment of these mice with viable BCG organisms 11 days before LPS administration renders them sensitive to the lethal effects of a highly purified, phenol-extracted LPS. Other in vivo responses to LPS are increased in BCG-infected C3H/HeJ mice in parallel with enhanced lethality. These include 1) the elevation of serum interferon, 2) the production of the acute phase reactant, serum amyloid A (SAA), and 3) hypoglycemia. However, BCG infection has only a minimal effect on anti-LPS antibody production. BCG-infected C3H/HeJ mice approach the LPS sensitivity of normal C3H/HeN mice, but the enhanced LPS sensitivity is transient and decreases over a 2-month period. The ability of BCG to induce LPS sensitivity in C3H/HeJ mice demonstrates that LPS unresponsiveness is not due to an absolute defect in this strain, but rather, a partially reversible state of hyporesponsiveness. In addition, these findings, in conjunction with other observations, suggest that the enhancement of LPS sensitivity induced by BCG infection is mediated primarily through an effect on T cells and/or macrophages rather than B lymphocytes.

Animals↗