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Biomedical subjects

D G Remick

Publications and source records attributed to D G Remick.

157 records · Page 9Linked to original sources
PubMed1987

Acute in vivo effects of human recombinant tumor necrosis factor.

Tumor necrosis factor is a peptide cytokine that induces hemorrhagic necrosis of some tumors and is responsible for the severe cachexia observed in advanced infectious diseases. We evaluated the acute effects of intravenous administration of purified human recombinant tumor necrosis factor in mice. With as little as 0.01 microgram/mouse (0.00045 mg/kg) a peripheral blood lymphopenia and neutrophilia developed as determined by flow cytometric analysis. At 1 microgram/mouse, the lymphopenia was both relative (21 +/- 3% versus 65 +/- 3%; p less than 0.001 treated versus control) and absolute (62 +/- 10 versus 229 +/- 29 X 10(4) cells/ml p less than 0.001). The neutrophilia was also relative (79 +/- 3% versus 34 +/- 3%; p less than 0.001 treated versus control) and absolute (237 +/- 26 versus 110 +/- 13 X 10(4) cell/ml; p less than 0.001). The neutrophilia was due to an increase in both mature and immature cells. At the higher doses the animals developed hypovolemic shock with an increased hematocrit and watery diarrhea occurred. Microscopic examination of the small bowel disclosed necrosis of the villi. Ultrastructural studies of the small bowel confirmed the necrosis and also showed severe endothelial cell damage, pyknotic nuclei, exocytosis of Paneth cell granules, and extravasation of red blood cells and neutrophils into the interstitium. A vascular leak syndrome developed with preferential fluid loss into the small and large bowel. These data demonstrate the potent in vivo effects of purified human recombinant tumor necrosis factor.

Animals↗
PubMed1986

Tumor necrosis factor-induced alterations in circulating leukocyte populations.

Tumor necrosis factor is a potent agent possessing diverse biological functions. We investigated the effects of intravenous administration of human recombinant tumor necrosis factor (TNF) on immune cell populations in CBA/J mice. The animals developed a significant lymphopenia and neutrophilia both reaching a maximum at 4 hours post-injection with a trend towards resolution to normal values by 6 hours. The lymphopenia was both relative and absolute. Similarly, the neutrophilia was both relative and absolute and was due to the presence of both immature and mature neutrophils. As the neutrophilia and lymphopenia occurred concomitantly, there was no difference at any time point in the total number of peripheral blood white cells. Extensive controls were done to rule out LPS contamination in the TNF preparation. These data demonstrate the potent effects of intravenous administration of human recombinant tumor necrosis factor on peripheral blood constituents.

Animals↗
PubMed1986

Release of interleukin-1 by peripheral blood mononuclear cells in patients with tuberculosis and active inflammation.

Peripheral blood monocytes from patients with active tuberculosis and acute inflammatory disease showed spontaneous interleukin-1 production when compared with those from control patients or healthy controls. Moreover, interleukin-1 production appeared to be a more specific indicator of active disease than were other commonly used indices, such as the erythrocyte sedimentation rate and serum C-reactive protein levels.

Acute Disease↗
PubMed1986

Modulation of murine schistosomiasis by exogenously administered prostaglandins.

The effect of parenteral administration of prostaglandins, 15-(s)-15-methyl PGE1 (M-PGE) and PGF2 alpha (PGF) on the pathophysiologic manifestations of active murine Schistosoma mansoni infection was examined. Both M-PGE and PGF resulted in a nearly 50% suppression of granuloma size following a 7-day course of treatment. M-PGE and PGF appeared to act by different mechanisms. The former caused a broad-spectrum immunosuppression manifested as reduced splenomegaly, B-cell proliferation, and antigen-specific interleukin-2 (IL-2) production as well as decreased granuloma macrophage Ia antigen expression, superoxide anion (O2-) production, and interleukin-1 (IL-1) production. In contrast, PGF did not ameliorate splenomegaly, but caused increases in splenic asialo-GM1 (natural killer cells) and L3T4 (helper) positive T cells. Prostaglandin F also reduced IL-2 production, but to a lesser extent that M-PGE. Although PGF caused reduced granuloma macrophage Ia expression and O2- production, it did not suppress IL-1 production. Overall, these data show that PGs can significantly modulate immunopathologic events in chronic granulomatous disease states.

Animals↗
PubMed1984

Benign polyps with prostatic-type epithelium of the urethra and the urinary bladder. A suggestion of histogenesis based on histologic and immunohistochemical studies.

The clinicohistologic features of seven urethral and four urinary bladder polyps with prostatic-type epithelium are described. The average age of the patients was 50 years. Seven patients had prior cystoscopies and in none of them was the lesion noted initially. Histologically the lesions were papillary or polypoid and the surface was lined predominantly by prostatic-type epithelium with interspersed transitional epithelial cells or by transitional epithelium with interspersed prostatic-type epithelial cells. The prostatic-type columnar cells contained foamy, faintly eosinophilic cytoplasm, which stained strongly for prostate specific antigen and prostatic acid phosphatase. In all the lesions, there were prostatic acini in the underlying fibrovascular stroma, which was devoid of smooth muscle. The intermingling of prostatic-type cells and transitional epithelium, on the surface of the polyps, the absence of lesions at previous cystoscopies, the coexistence of cystitis cystica glandularis (a metaplastic lesion), and the older age group of our patients suggest that the prostatic-type epithelium in the polyps of urethra and urinary bladder is an acquired lesion, most likely a metaplastic response of transitional epithelium, which embryologically was multipotential.

Acid Phosphatase↗
PubMedDate not supplied

Local and systemic concentrations of tumour necrosis factor-alpha, interleukin-6 and interleukin-8 in bacterial osteomyelitis.

Osteomyelitis is a major cause of morbidity worldwide but there are few data investigating pathogenesis of infection and no investigations into local secretion of proinflammatory cytokines in patients. Tumour necrosis factor-alpha (TNF), interleukin (IL)-6 and IL-8 concentrations were measured in pus of infected bone from 30 Zambian patients with chronic osteomyelitis (principally caused by Staphylococcus aureus), in plasma, and after lipopolysaccharide stimulation of whole-blood leucocytes. Patients had reduced body mass index compared to controls (P = 0.025) and an acute-phase response. Elevated concentrations of proinflammatory cytokines were detected in bone compared to plasma (all P < 0.0002). Bone IL-8 concentrations were greater than IL-8 levels after lipopolysaccharide stimulation of whole blood (P < 0.01). In contrast, systemic and ex-vivo-stimulated concentrations of proinflammatory cytokine were similar in patients and controls, despite differences in body mass index and an acute-phase response. In summary, we observed marked local TNF, IL-6 and IL-8 secretion in established bacterial osteomyelitis without systemic cytokine release.

Adolescent↗
PubMedDate not supplied

Interleukin-8 levels and activity in delayed-healing human thermal wounds.

There are numerous causes for slow or delayed wound healing. Because slowly healing wounds are often inflamed, we quantitated the inflammatory chemokine, interleukin-8, produced by slowly healing human burn wounds and compared this to interleukin-8 from healed wounds and normal intact skin. Interleukin-8 levels were increased significantly in unhealed wounds (19.7 ng/ml) compared to healed wounds (7.7 ng/ml) or normal skin (5.7 ng/ml). Interleukin-8 in these ranges was added to adult human keratinocytes and fibroblasts. Interleukin-8 significantly decreased keratinocyte replication but had no effect on fibroblast replication. The rate or final degree of fibroblast populated collagen lattice contraction was inhibited at interleukin-8 concentrations between 10 and 30 ng/ml, but not altered at concentrations below 10 ng/ml and above 100 ng/ml. The concurrent application of indomethacin at 10 microg/ml reversed this interleukin-8 induced inhibition. Interleukin-8 inhibited myosin ATPase activity, apparently by reducing the phosphorylation of nonmuscle myosin light chain. We conclude that elevated levels of interleukin-8 may be found during delayed healing, and these elevated interleukin-8 levels may directly contribute to retarded wound closure.

Adult↗
PubMedDate not supplied

Antibodies against tumor necrosis factor prolong cardiac allograft survival in the rat.

Tumor necrosis factor (TNF)-alpha has significant biologic actions in many circumstances, such as infectious diseases, ischemia/reperfusion injury, and delayed-type hypersensitivity reactions. Based on the hypothesis that manipulation of TNF can play an important role in treatment of heart transplant rejection, the objective of this study was to determine whether anti-TNF antibodies could prolong cardiac allograft survival. Hearts from brown rats were transplanted to the necks of recipient Lewis rats. Graft survival was determined by direct palpation of the heart; complete graft rejection was defined by cessation of contraction. In untreated rats, the hearts were rejected 6.8 +/- 0.6 days (n = 10; mean +/- SEM) after transplantation. The mononuclear cell infiltrate in the transplanted hearts stained intensely for TNF by immunohistochemistry, indicating that TNF was present within the inflammatory cells associated with the rejection process. In rats receiving a single injection of anti-TNF antibody at the time of transplantation (n = 6), however, graft survival was nearly doubled (12.7 +/- 1.4 days; p less than 0.001 vs controls). Prolonged cardiac graft survival was also evident if the anti-TNF treatment was delayed until 1 day (n = 5; rejection at 16.2 +/- 2.4 days; p less than 0.001 vs controls) or even 3 days after transplantation (n = 5; rejection at 11.4 +/- 2.3 days; p less than 0.005 vs controls). Treatment at 5 days after transplantation, however, was not effective (n = 3; rejection at 7.7 +/- 0.6 days; p, not significant vs controls). The data indicate that a single bolus of anti-TNF antibodies can delay heart transplant rejection, even when administered up to 3 days after implantation, supporting the potential utility of anti-TNF therapy for treatment of heart transplant rejection.

Animals↗