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In 1712 the 'ma'amad' of the Spanish-Portuguese community of Amsterdam excommunicated three of its members on charges of Karaism: David Mendes Henriquez (also known as David Almanza) and the brothers Aaron and Isaac Dias da Fonseca. In Amsterdam, as well as elsewhere in Western Europe, Sephardic Jews were impressed by the ideal image of Karaism as it was projected in the Christian Hebraist literature beginning in the mid-17th century. The views of Richard Simon enjoyed particular currency. Some neo-Karaites turned away from Judaism and espoused Calvinist Christianity.

Cells of the dental papilla are capable of odontoblastic, fibroblastic, and endothelial differentiation and formation of dentin and the dental pulp. In the present study dental papilla cells, obtained from human tooth buds (HDP cells), were cultured in vitro through 3 to 7 passages. After exposure to prostaglandin E2 there was a marked decrease in intracellular cyclic AMP (cAMP) levels as compared to hormone-free controls. Parathyroid hormone and calcitonin had stimulatory effects with 1 and 2 log increases in cAMP, respectively. The HDP cells showed moderate activity of alkaline phosphatase, 1 log higher than that of hamster kidney fibroblasts (BHK 13) and 1 log lower than that of osteoblastic osteosarcoma cells (ROS 17/2). When cultured for 4 or 8 wk in diffusion chambers (DC) implanted in athymic mice, many of the HDP cells underwent odontoblastic morphodifferentiation with very long, single processes extending into the matrix. This matrix contained banded and unbanded collagen fibers. Neither light nor electron microscopy of the DC content revealed mineral deposits. These results suggest that HDP cells have an intrinsic potential for partial odontoblastic differentiation; inductive signals like those originating from odontogenic epithelium are probably essential for the completion of hard tissue formation.

In 1712 the ma'amad of the Spanish-Portuguese community of Amsterdam excommunicated three of its members. David Mendes Henriquez (also known as David Almanza) and the brothers Aaron and Isaac Dias da Fonseca. All three were accused of belonging to the Karaite sect. During the 17th century the Sephardic communities of Western Europe frequently applied the appellation 'Karaite' in a metaphoric sense, designating thereby those of heterodoxic tendencies who denied the Oral Tradition and rabbinic authority. Actual contacts between Sephardic Jewry and Karaite communities were in fact most uncommon. The case before us, however, represents an explicit link with Karaites. It appears that in Amsterdam as well as elsewhere in Western Europe Sephardic Jews were impressed by the ideal image of Karaism as it was projected in the Christian Hebraist literature beginning in the mid—seventeenth century. This literature frequently evinced a preference for 'Karaites' over 'Rabbinic Jews', by depicting th

Two boys aged six and four with the syndrome of hereditary resistance to 1,25-dihydroxyvitamin D3 with rickets alopecia and growth retardation are presented. After unsuccessful therapeutic trials with pharmacologic doses of vitamin D or its active metabolites, the patients were treated by long-term intracaval infusions of calcium through an implantable catheter. A total of 0.5 to 0.9 g of elemental calcium was infused daily for 18 months and the serum calcium concentration was maintained at 9 to 10 mg/dl. Bone pain subsided within one week of treatment. Serum phosphorus, immunoreactive parathyroid hormone, and 1,25-dihydroxyvitamin D concentrations and alkaline phosphatase activity were normalized within four to nine months. Radiographs of the knees and hands revealed progressive healing of rickets with complete resolution after one year of treatment. The patients gained 12 cm and 8 cm per year in height as compared with 3 cm and 2 cm, respectively, in the previous year. A transilial bone biopsy obtained from one patient prior to treatment revealed severe osteomalacia associated with osteitis fibrosa. A follow-up biopsy examined after 12 months of therapy showed almost complete healing of osteomalacia and normal mineralization. These observations indicate the following: (1) Long-term intracaval calcium infusions are an effective mode of therapy for these patients, and (2) When adequate serum calcium and phosphorus concentrations are maintained, healing of rickets and normal growth rate could be achieved even in the absence of a normal 1,25-dihydroxyvitamin D3 receptor-effector system.

Voluminous literature exists today on the involvement of cationic polyelectrolytes (CPs) in host and parasite interrelationships. It has been shown that CPs of neutrophil (1-14), eosinophil (15, 16), macrophage (17), and platelet (18) origins function as distinct microbicidal agents. These probably constitute a "secondary" defense line supplementary to the main oxygen-dependent microbicidal systems of "professional" phagocytes. CPs have, however, also been implicated as modulators of blood clotting (19) and fibrinolysis (20), as a permeability-enhancing factors (21-23), in mast cell degranulation and in histamine release (24), as pyrogenic agents (25), as enhancers of complementmediated lysis (26), as modulators of PMN adherence (27-29) and chemotaxis (30-34), and as modulators of endocytosis (35-45) to list only several of the properties ascribed to these agents. Since the effects of CPs probably involve the interaction, through electrostatic forces, with negatively charged sites on target cells (36), it is plausible that the complex polyelectrolytic milieu found in infectious and inflammatory sites might function to modulate and regulate several important interactions of the host with invaders (46-48). Although CPs are primarily recognized for their distinct killing properties (10-13), recent studies have suggested that CPs might also be involved in a variety of additional biological, biochemical, and immunopathological phenomena which are seldom discussed in the general context of host and parasite interrelationships. The present review deals primarily with the possible involvement of CPs (1) in endocytosis and in cell adherence, (2) as activators of the respiratory burst in "professional" phagocytes, (3) as activators of the autolytic wall enzymes in certain microbial species and its relation to bacteriolysis and to the pathogenesis of chronic inflammation induced by bacterial cell walls, and (4) as agents capable of modulating the pathogenicity of immune complexes. It was felt that a discussion of these "other" properties of CPs is timely as it may shed a new light on the role of surface charge in cell-to-cell interactions as seen in inflammatory and infectious sites.

GENERAL INTRODUCTION. The invasion of the tissues of a host by pathogenic microorganisms is usually followed by a series of sequential humoral and cellular events which include: the generation of chemotactic agents, the directional migration of leukocytes toward the invader, the opsonization of the agents by immunoglobulins and complement components, the intemalization of the agents within phagolysosomes. and eventually by the killing and biodegradation of the ingested agents. The perturbation of the leukocytes membranes by opsonized micro- organisms as well as by a variety of cytolytic agents generated by bacteria is also accompanied by a series of biochemical events which include an “oxygen burst" which culminates in the generation of oxygen radicals, some of which are directly involved in the killing of the ingested agents. Concomitantly with the activation of the oxygen metabolism, granulocytes (PMN)f and macrophages (MQ)f also generate chemiluminescence (CL) which is believed to be a natural consequence of the redox met mbrane perturbation due to phagocytosis. lt may involve the generation of a species of singlet oxygen and hydroxyl radicals or electronically excited carbonyl groups which relax with light emission. A relationship between CL and superoxide production has also been demonstrated by the reduction of CL which occurs following the addition of superoxide dismutase (SOD) to phagocytizing leukocytes. The CL signals which can be further amplified by luminol are also believed to be dependent upon myeloperoxidase (MPO)-catalyzed reactions and/or upon metabolism of arachidonic acid pathway(s). The luminol-de-pendent CL ( LDCL) reaction is currently employed to assess the opsonophagocytic properties of sera as we as for the evaluation of the membrane perturbation which is initiated, in leukocytes, by cytotoxic drugs, and by microbial toxins. ln addition to opsonized particles, a series of soluble ligands, i.e., chemotactic peptides, lectins, phorbol esters, calcium ionopohres, polyanethole sulfonate, and cationic polypeptides have all been shown to stimulate the oxygen burst and to generate CL in neutrophils, monocytes, and macrophages. Because of the relative ease and rapidity with which CL is measured in leukocytes, this method has also become a powerful tool to investigate host-and-parasite interrelationships and to assess defects in leukocyte functions (e.g. , chronic granulomatous disease of childhood (CGD) MPO deficiency, defects in complement components and in immunoglobulins, etc.). Recent studies from our laboratory have described a unique phenomenon which showed that a variety of microbial species can be very effectively “opsonized” by cationic proteins rich in arginine (e.g., histones. poly-L-arginine - PARG). Such opsonized microorganisms are readily internalized not only by "professional" phagocytes (PMNs and macrophages) but also by epithelial cells and by fibroblasts. We have postulated that perturbation of the mammalian cells by the highly-charged polyelectrolytes, coated upon particles, delivers a signal (through electrostatic interactions) to the cytoskeleton resulting in the invagination of the membrane and the formation of a phagocytic vacuole. This phenomenon mimics the cellular events that take place following the stimulation of the leukocyte membrane by antibody and complement-coated particles which function through the F and Cb receptors. Thus, the polycationic ligands may represent "archaic" antibodies capable of stimulating certain membrane sites probably nonspecifically (see Section A.l). Our studies further postulated that if leukocytes “recognize" cationic charges upon particles and respond to them by phagocytosis, such coated particles should also be able to trigger an “oxygen burst" in a fashion similar to that induced either by antibody-coated particles or by other membrane- active agents. Indeed, we have demonstrated tnat very intense LDCL and superoxide production ls triggered in blood leukocytes following stimulation with bacteria and zymosan particles which had been precoated with arginine rich histon PARG and paradoxically also by the anionic polyelectrolytes,.|iquoid. anddextransulfatc. The intensity of the CL signals obtained exceeded by many magnitudes those induced by antibody-coated particles. These findings further suggested that the stimulation of the leukocyte membrane, either simultaneously or sequentially by mixtures of different ligands, each recognizing a different membrane site, may perhaps culminate in a synergistic metabolic response. Such "multiple hits" may therefore generate large quantities of oxygen radicals and CL, presumably due to a more efficient activation of the membrane oxidase and a better assembly of the electron transport system leading to the generation of superoxide. We have chosen to examine agents like the chemotactic peptide F-Met-Leu-Phe (FMLP), a variety of lectins, calcium ionophore, PMA, liquoid, and poly ot-cationic peptides as probes for the stimulation of LDCL and superoxide production by human PMN. We have shown that whereas each ligand alone induced only a very moderate LDCL response in leukocytes, very intense CL signals were generated if the various ligands were employed as “cocktails, suggesting multiple mechanisms of activation of the oxygen metabolism in leukocytes (see also Reference 27). Since inflammatory exudates which accumulate following microbial proliferation in tissues are known to be rich in both cationic and anionic polyelectrolytes, we also postulated that some of these agents may coat either the surface of the leukocytes or the surface of the microorganisms, or both. and thus modulate mutual recognitions leading either to enhanced or depressed membrane perturbation. These changes may be monitored by CL and by the production of superoxide. The present report further expands our observations on the multiple roles played by polycationic and polyanionic agents and of "cocktails" of soluble ligands in the stimulation of the generation of LDCL and superoxide by human blood luekocytes and by mosue peritoneal macrophages, with an emphasis on the luekocyte-bacteria interactions in inflammation.

Photohydrogenation of phenylacetylene and methylphenylacetylene was accomplished in a H2O-cyclohexane system, using tris(bipyridine)ruthenium Ru(bpy)32+ (bpy = 2,2'- bipyridine) as a photosensitizer, N,N'-dialkyl-4,4'-bipyridinium (viologen), CnV2+, as a charge relay, Na2EDTA as a sacrificial electron donor, and a Pt or Pd colloid stabilized in the org. phase as a hydrogenation catalyst. The photogenerated bipyridinium radical cations undergo induced disproportionation in the water-oil two-phase system, and the 2-electron charge relay CnV: is the active photoproduct that charges the metal colloid and generates metal-bound H atoms that are active in the hydrogenation of the substrate. The Pt and Pd colloids differ in their effectiveness in the generation of metal-bound H atoms. While Pt is a superior catalyst in this function, Pd is superior to Pt in the activation of the substrate toward hydrogenation. Use of a mixt. of Pt and Pd colloids in a water-oil 2-phase system shows a synergetic catalytic activity in the photohydrogenation of the acetylenic substrates. [on SciFinder(R)]

Considerable attention has been focused on the role of electrostatic charge in the pathogenesis of immune complex-mediated tissue injury. The authors have examined the ability of cationic (histone, polyhistidine, polyarginine) and anionic (polyanetholsulfonate) polyelectrolytes to modulate acute immune complex-mediated tissue injury. Tissue injury elicited in rats by the reversed dermal Arthus reaction was increased 26-43% by addition of polyelectrolytes to antibody prior to its intradermal injection. Kinetic studies using 111In-labeled neutrophils indicated that the enhanced tissue injury was not the result of increased influx of neutrophils. Infusion of polyethylene glycol-conjugated superoxide dismutase prior to induction of the Arthus reaction resulted in 40-68% suppression of tissue injury. Concomitant in vitro functional studies (enzyme secretion, O-2 and H2O2 generation, and chemiluminescence) of rat neutrophils demonstrated that addition of polyelectrolytes to preformed immune complexes (IgG-bovine serum albumin) resulted in marked increases in O-2, H2O2, and chemiluminescence, but no increases in enzyme secretion, compared with neutrophils stimulated with immune complexes alone. The cationic polyelectrolytes did not alter the capacity of preformed immune complexes to activate complement in vitro. These studies suggest that both cationic and anionic polyelectrolytes can increase the pathogenic potential of immune complexes and that this modulation is, at least in part, mediated by enhanced generation of toxic oxygen-derived metabolites by neutrophils.