Present and emerging applications of polymeric biomaterials

An important trend in biomaterials research and development is the synthesis of polymers, which combine capabilities of biologic recognition ('biomimetic') with special physicochemical properties of the synthetic polymer system. For example, an antibody may be conjugated to the backbone of a polymer which precipitates upon small changes in pH, temperature, or ionic strength. Crosslinked gels may also be synthesized from such polymers, and a biomolecule such as an enzyme may be chemically or physically entrapped in these gels. Such gels will shrink and swell in response to small changes in environmental stimuli. Another approach is to 'engineer', perhaps via computer-aided molecular design, new artificial biomimetic systems by exact placement of functional groups on rigid polymer backbones, crosslinked structures, or macromolecular assemblies. In this way, biocatalytic functioning or biorecognition similar to enzymes and antibodies can be achieved without the inherent instability often encountered with the native biomolecules or assemblies. In addition to these synthetic approaches, new and exciting analytical tools, such as the scanning tunnelling microscope and the atomic force microscope, are permitting visualization of individual and small clusters of proteins and other biomolecules on surfaces. Cell attachments and spreading may also be visualized at various depths within the cell using the confocal laser microscope. Such analytical techniques can lead to important new knowledge about biologic interactions with biomaterials, and, therefore, to development of even more biocompatible implants and devices. This paper overviews the field of polymeric biomaterials and highlights the important emerging trends in synthesis and analysis of these materials.     

Pollution prevention as a market-enhancing strategy: a storehouse of economical and environmental opportunities

EPA's (Environmental Protection Agency) Green Lights Program for energy-efficient lighting illustrates the economic benefits and the market-transforming value of a pollution prevention philosophy. Using technologies available today, and assuming current prices, this program is expected to reduce air pollution 5%, while saving the nation's businesses up to 20 billion in electric bills every year. However, these pollution prevention and savings estimates may be low. As Green Lights transforms the market for lighting services by creating a higher demand for better technologies at lower costs, the program will likely achieve even larger pollution reductions and electricity savings.     

Some epidemiological and scanning electron microscopic features of crazing of the dental enamel of Polynesians

The prevalence of enamel crazing was determined from the maxillary incisors and canines of 1,109 Tongan residents aged 5-20 years, 1,417 Cook Island residents aged 6-20 years, 520 French Polynesian residents aged 10-15 years, and 92 New Zealand-born and -resident Polynesians aged 11-18 years. Crazing occurred in 22 percent of Tongans, 7 percent of Cook Islanders, but not in French Polynesians or New Zealand-born Polynesians. Cracks become clinically apparent at about 8 years of age; were more common in males than females; and became more common with increasing age. The central incisors were the most commonly affected of the maxillary anterior teeth. Cross-sections of teeth with crazing viewed by light and scanning electron microscopy appeared similar to other stained cracks. The indications are that crazing is a post-eruptive change caused by trauma from local environmental factors resulting in stress fractures. The significance of crazing on enamel structure and strength is unknown, but it is probably minor without long-term disadvantages. The prevalence of crazing may prove useful in anthropology as an indicator of the use of teeth as tools and in assessing the "modernisation" of a population.     

Cellular immunity in Guamanians with amyotrophic lateral sclerosis and Parkinsonism-dementia.

To test the hypothesis that host resistance factors may be abnormal in Guamanians in whom amyotrophic lateral sclerosis and Parkinsonism-dementia develop, cellular immunity was evaluated in both diseases and compared to that of Guamanians with other nervous-system diseases, normal adult Guamanians and non-Guamanians with amyotrophic lateral sclerosis and Parkinsonism. Diminished responses to skin-test antigens, lymphopenia, diminished per cent and total T cells and, less frequently, decreased mitogen responses were seen in Guamanian patients with amytorophic lateral sclerosis and Parkinsonism-dementia but not in the other patient or normal groups. Guamanian patients with amyotrophic lateral sclerosis and diminished cellular immunity had an increased frequency of HLA-Bw35 (P less than 0.005) and shorter mean duration of disease (P less than 0.05) than those with normal cellular immunity. In Parkinsonism dementia diminished cellular immunity was less strongly associated with HLA-BW35 (P less than 0.05) and was not associated with differences in duration of disease. Normal Guamanians and those with other nervous-system diseases showed no association of diminished cellular immunity with HLA-Bw35. The association appeared disease-related, with onset concomitant with the neurologic expression of Guamanian amyotrophic lateral sclerosis and Parkinsonism-dementia.     

Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy

A deficiency of the protein dystrophin has recently been shown to be the probable cause of Duchenne's muscular dystrophy. We sought to determine the relation between the clinical phenotype and the status of dystrophin in muscle-biopsy specimens from 103 patients with various neuromuscular disorders. We found very low levels (less than 3 percent of normal levels) or no dystrophin in the severe Duchenne phenotype (35 of 38 patients), low concentrations of dystrophin in the intermediate (outlier) phenotype (4 of 7), and dystrophin of abnormal molecular weight in the mild Becker phenotype (12 of 18). Normal levels of dystrophin of normal molecular weight were found in nearly all the patients (38 of 40) with 20 other neuromuscular disorders we studied. These data show the clinical consequences of both quantitative alterations (in Duchenne's and intermediate dystrophy) in a single protein. The biochemical assay for dystrophin should prove helpful in delineating myopathies that overlap clinically with Duchenne's and Becker's dystrophies, and it shows promise as an accurate diagnostic tool.     

Elevated fibroblast growth factor-23 in hypophosphatemic linear nevus sebaceous syndrome

We report on an adolescent who experienced the onset of linear nevus sebaceous syndrome (LNSS) prior to 1 year of age. At 7 years of age he was diagnosed to have hypophosphatemic rickets. He was suboptimally controlled with phosphate and calcitriol treatment and sustained numerous insufficiency fractures ipsilateral to the linear sebaceous nevus. Fibroblast growth factor-23 (FGF-23), the phosphaturic peptide, was elevated in the plasma. Treamtent with the somatostatin agonist, octreotide, and excision of the nevus were followed by normalization of FGF-23 and clinical improvement. The patient also had hyperimmunoglobulinemia E, which responded to octreotide and surgery. We speculate that in some patients with LNSS there may be more than one mediator of hypophosphatemia and that FGF-23 is the mediator of hyperphosphaturia in this and other hypophosphatemic syndromes.     

Family interaction and the development of borderline personality disorder: a transactional model

Although no prospective epidemiological studies have evaluated the relationship between family interactions and the development of borderline personality disorder (BPD), there is considerable evidence for the central role of family interactions in the development of BPD. This paper describes the role of family interactions or processes, especially those that might be regarded as invalidating or conflictual, negative or critical, and the absence of more validating, positive, supportive, empathic interactions, in the development of BPD. Perhaps more importantly, the proposed model considers how these parental and family behaviors transact with the child's own behaviors and emotional vulnerabilities, resulting in a developmental model of BPD that is neither blaming of the family member with BPD nor of her or his parents and caregivers, and has important and specific implications for both prevention and intervention.     

Anti-citrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis: specificity and relation with rheumatoid factor

Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific and sensitive markers for rheumatoid arthritis (RA). For instance, for the anti-CCP2 assay, sensitivities ranging from 55% to 80% and specificities ranging from 90% to 98% have been reported. Despite their high specificity, recent reports have suggested that ACPA may be found in some patients with other rheumatic autoimmune diseases, including psoriatic arthritis, systemic lupus erythematosus and Sj?gren's syndrome. Also, the differences between the classical rheumatoid factor (RF) and ACPA, as well as the complementarity between both tests have recently been demonstrated more clearly. Indeed, both antibody systems have a different association with specific RA features like extra-articular manifestations, a different association with the HLA shared epitope and, behave differently following anti-TNF therapy.     

Murine splenic hematopoietic subpopulations: the enlarged undifferentiated subset in New Zealand black mice is multipotent stem cells.

We recently reported that a significant population of the murine splenic non-T, non-B "null" cell compartment consists of non-lineage-specific, undifferentiated cells which are in the G0 and G1 phases of the cell cycle and that their numbers are particularly high in the spleens of New Zealand Black mice. A highly enriched population of these non-lineage-specific cells obtained by successive elimination of differentiated cells was further purified to homogeneity by fluorescence-activated cell sorting. The morphologic, phenotypic, and histochemical characteristics of this purified population suggest that these cells may be primitive hematopoietic stem cells. The germ line configuration of the genomic DNA establishes that these are uncommitted stem cells. In vivo, these cells form day 12 colonies in the spleen and liver of lethally irradiated recipients and confer radioprotection. These cells also differentiate into T- and B-cell lineages and reconstitute the immunodeficiency in mice with severe combined immunodeficiency. In response to a combination of a very few early-acting lymphokines and/or stromal cell-conditioned medium in vitro, these cells differentiate into both myeloid and lymphoid cell types. More of these cells are obtained from the enlarged spleens of New Zealand Black mice than from those of BALB/c mice. The presence of a comparatively higher number of stem cells in the spleen than in the marrow or fetal liver provides an alternative, and possibly superior, source of uncommitted stem cells for a variety of experimental investigations or therapeutic manipulations.