Bernice Noble

Collagen as an Implantable Material in Medicine and Dentistry

Collagen is a highly versatile material, extensively used in the medical, dental, and pharmacological fields. Collagen is capable of being prepared into cross-linked compacted solids or into lattice-like gels. Resorbable forms of collagen have been used to dress oral wounds, for closure of graft and extraction sites, and to promote healing. Collagen-based membranes also have been used in periodontal and implant therapy as barriers to prevent epithelial migration and allow cells with regenerative capacity to repopulate the defect area. It has been hypothesized that membrane regenerative techniques facilitate the natural biological potential by creating a favorable environment for periodontal and peri-implant regeneration. Due to the enormous potential of collagen-based regenerative barriers, clinicians may benefit from a review of potential applications of implantable collagen and knowledge of collagen preparation and membrane types as well as from as awareness of the functional and degradation properties of those materials.

Neuronal-associated tumor necrosis factor (TNFα): its role in noradrenergic functioning and modification of its expression following antidepressant drug administration

Tumor necrosis factor-alpha (TNF alpha) and the alpha 2-adrenergic agonist clonidine regulate norepinephrine (NE) release from noradrenergic nerve terminals in the central nervous system (CNS). In the present study, superfusion and electrical field stimulation were applied to a series of rat hippocampal brain slices in order to investigate the regulation of [3H]-NE release. NE release had been previously determined to be decreased by TNF alpha in a concentration-dependent manner, an effect which was potentiated by the alpha 2-adrenergic antagonist idazoxan. Presently, we demonstrate that similar to alpha 2-adrenergic activation, TNF alpha regulation of NE release in a region of the brain rich in noradrenergic nerve terminals, is dependent upon the frequency of electrical stimulation applied to the hippocampal slice. Furthermore, immunoperoxidase staining has verified our previous findings of constitutive TNF alpha protein in the rat brain. Staining for TNF alpha appears to be largely localized to neurons and neuronal processes, further substantiating the proposal that TNF alpha is either synthesized de novo or is accumulated in and released by neurons. After administration of the tricyclic antidepressant desipramine, tissue sections obtained from the rat hippocampus and locus coeruleus are devoid of neuronal-associated TNF alpha immunoreactivity. TNF alpha localization in neurons and its modification of NE release comparable to alpha 2-adrenergic receptor activation, explains a functional role for the cytokine as a neuromodulator in the CNS.

Role of Allergy in Nasal Polyposis: A Review

We propose a multivariate theory for the pathogenesis of nasal polyps. Turbulent flow of air in the lateral wall of the nose or viral-bacterial-host interactions produce an inflammatory change in the mucosa of the lateral wall of the nose. Ulceration and prolapse of the submucosa with reepithelialization and new gland formation may then follow. The structural cells of the nasal polyp, including epithelial cells and fibroblasts, have the ability to produce messenger RNA for granulocyte-monocyte colony-stimulating factor and other cytokines. Stimulation of such an effector capability by structural cell-derived cytokines would undoubtedly represent a major amplification pathway of the inflammatory response in nasal polyps. Allergy may be one mechanism for the development of this cascade of events. This microenvironmental structural inflammatory response in the nasal polyp, in turn, can affect the bioelectric integrity of the Na+ and Cl- channels at the luminal surface of the respiratory epithelial cell. The change in the Na+ absorption, which has been demonstrated in our studies, may result in an increased movement of water into the cell and into the interstitial fluid. The resultant edema can lead to growth and enlargement of the nasal polyp. Finally, the rapid recurrence of nasal polyps despite adequate surgery may reflect some intrinsic phenotypic characteristic of nasal epithelial cells in the lateral wall of the nose, which is likely to be under genetic control.

Experimental Chronic Serum Sickness in Rats

This article describes a method of immunization that produces chronic serum sickness in rats within a relatively short time. Fisher rats, which were immunized subcutaneously three times with bovine serum albumin (BSA) in adjuvant, responded with high titers of antibodies to BSA. 2 weeks after the third subcutaneous immunization, daily increasing amounts of BSA were injected either intraperitoneally or intravenously. When an intravenous dose of 2mg of BSA was reached, the rats were given daily intravenous injections of BSA for several weeks. This procedure, which avoided death from anaphylaxis, induced severe proliferative glomerulonephritis in all the rats and produced deposition of antigen-antibody complexes in many other organs besides the kidney. This highly reproducible model of experimental chronic serum sickness in inbred animals may have applications for the study of the mechanisms of immune complex disease.

Collagen: an overview.

Collagen is a versatile material with biological properties that make it useful for the fabrication of implantable devices in medicine and dentistry. In this article we review collagen biosynthesis, structure, and types, as well as the properties that make it compatible with human tissues.

gb-adrenergic receptor regulation of macrophage-derived tumor necrosis factor-α production from rats with experimental arthritis

Prostaglandin E2 (PGE2) and β-adrenergic agonists can suppress lipopolysaccharide-induced tumor necrosis factor-α (TNF) production from elicited macrophages. We assessed the responsiveness of rat peritoneal macrophages to PGE2 and the β-adrenergic agonist isoproterenol during immunologically-mediated arthritis. We assessed macrophage sensitivity to these mediators from resident macrophages and macrophages elicited with either streptococcal cell wall or complete Freunds adjuvant. Peritoneal macrophages were obtained from female Lewis rats that were (1) injected with complete Freunds adjuvant and non-arthritic (CFA); (2) injected with streptococcal cell wall and arthritic (ART); (3) injected with streptococcal cell wall and non-reactive (NON) and (4) non-elicited resident macrophages (RES). When challenged with graded concentrations of lipopolysaccharide (0.1 to 10,000 ng/ml), macrophages obtained from each group of rats released TNF in a concentration-dependent manner, with macrophages from arthritic rats (ART) producing the greatest amount of TNF (p < 0.001). While PGE2 suppressed lipopolysaccharide (100 ng/ml) stimulated TNF production in a concentration-dependent manner in all groups, the greatest sensitivity to PGE2 was observed with macrophages obtained from rats which received streptococcal cell wall when compared to both complete Freunds adjuvant-elicited and resident macrophages (p < 0.05). The β-adrenergic agonist isoproterenol also inhibited lipopolysaccharide-stimulated TNF production from macrophages in all groups. In addition, the specific β2-adrenergic antagonist, ICI 118.551, shifted isoproterenol concentration-effect curves to the right (p < 0.01). Minimal responsiveness to isoproterenol was observed with resident peritoneal macrophages. Maximum isoproterenol-induced inhibition of TNF production was observed with complete Freunds adjuvant-elicited macrophages, and significantly less in macrophages of streptococcal cell wall-injected rats. Of particular interest, macrophages obtained from streptococcal cell wall-injected rats, which became arthritic, were significantly less sensitive to isoproterenol than those which did not develop arthritis (p < 0.02). In addition, these changes in sensitivity were not reflected by changes in the sensitivity of both CFA and ART groups to dibutyryl cAMP. The present study demonstrates a shift in the balance between inhibitory mediator responses in rats inoculated with one of two different adjuvants. These investigations support the role of PGE2 and a neurotransmitter as immunomodulating compounds which may effectively maintain an inflammatory lesion such as arthritis.

Antibody-mediated injury to proximal tubules in the rat kidney induced by passive transfer of homologous anti-brush border serum

Abstract Study of the natural history of Heymann nephritis in rats has led to the suggestion that antibodies to brush border are responsible for injury to proximal tubules. To obtain direct evidence that antibodies to brush border are cytotoxic to cells of the proximal tubular epithelium, passive transfer experiments were performed. Rats with serum sickness glomerulonephritis were recipients of homologous anti-brush border serum. Forty-eight hours after the first injection of anti-brush border serum, immunoglobulin was bound to the luminal border of proximal tubules. Fixation of immunoglobulin was associated with loss of microvilli and proliferation of cells of the tubular epithelium. The changes in proximal tubules observed in passive transfer experiments were similar to those seen in rats with Heymann nephritis and were not observed in animals which received injections of normal rat serum. It appears that damage of renal tubules may be the consequence of deposition of antibodies along the plasma membrane of tubular cells.

Glomerular macrophage proliferation in experimental immune complex nephritis

In immune complex nephritis, glomerular hypercellularity is known to result from the proliferation of intrinsic cells and from the infiltration of mononuclear cells, primarily macrophages. An immunohistochemical double-labeling procedure was used to determine whether macrophages were among the cells which may undergo mitosis within the glomerular tuft. The monoclonal antibody ED1 served as a macrophage marker; cells in the S-phase of mitosis were recognized by uptake of bromodeoxyuridine. Glomerular proliferation was studied in chronic serum sickness of LEW rats, an animal model of immune complex nephritis for which the relationship between immunopathology and pathophysiology has been well described. In normal glomeruli, resident mesangial macrophages accounted for an unexpectedly large proportion (greater than or equal to one-third) of the total mitotic activity. In immune complex glomerulonephritis, the rate of glomerular macrophage proliferation increased rapidly just at the onset of proteinuria and remained high throughout the remaining course of disease. Glomerular macrophages from rats with proliferative nephritis also divided more vigorously than normal in short term culture in vitro, while persistently expressing abnormal surface marker phenotypes. The proliferation of mesangial macrophages appears to be a prominent feature of the normal process of glomerular cell renewal. In hypercellular glomeruli, vigorous local proliferation could greatly amplify the potential of macrophages to cause damage.

Immunologically mediated lesions of kidney tubules and interstitium in laboratory animals and in man

ConclusionIn recent years, animal models of TI nephritis attributable to humoral immune mechanisms have become firmly established. Results of immunopathology studies indicate that similar mechanisms might be involved in a small fraction of human TI nephritides. In some patients the contribution of humoral immune mechanisms to TI lesions may not have been recognized in tissue specimens obtained at late stages of disease.In laboratory animals as well as in man insufficient information is available to appraise the possible significance of immediate-type hypersensitivity and cell-mediated immune reactions in the induction and perpetuation of TI lesions. More studies on these two immune effector mechanisms are needed to clarify the pathogenesis of TI nephritis that, in the majority of the patients, is still not understood.

Factors influencing susceptibility of LEW rats to Heymann nephritis.

Although most LEW rats develop the proteinuria of Heymann nephritis (HN) within 2 months after immunization with Fx1A, protein excretion of some animals remains normal. We have compared nonproteinuric rats with those that developed HN in order to identify factors that influence susceptibility to immunologically medicated kidney disease. In the primary response to Fx1A, immunofluorescence tests showed that antibrush border titers in serum and immunoglobulin deposition in vivo were similar in all rats. However, complement was detected only in rats with proteinuria. Reimmunization with Fx1A at 30 weeks stimulated anamnestic antibody responses in all rats. Following reimmunization, 60% of nonproteinuric rats developed severe HN with an unusually rapid (1 week) onset. Once again, complement was present only in glomeruli of rats with proteinuria. It appears that titers of antibodies to brush border, measured by immunofluorescence tests, are not an index of the pathogenicity of the immune response to Fx1A. Immunological memory, leading to rapid expression of autoimmune disease upon reexposure to antigen, can be established by a primary immunization that does not produce clinical symptoms. Abnormal urine protein composition may provide a clue to subclinical immunopathology of the kidney.