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Biomedical subjects

L Jacobson

Publications and source records attributed to L Jacobson.

At least 109 records · Page 6Linked to original sources
PubMed1994

Response to human acetylcholine receptor alpha 138-199: determinant spreading initiates autoimmunity to self-antigen in rabbits.

NZW rabbits immunised with a mixture of synthetic peptides representing alpha 138-199 of the human acetylcholine receptor (AChR) alpha-subunit exhibited clinical, biochemical and electrophysiological signs of experimental autoimmune myasthenia gravis (EAMG), with raised levels of anti-rabbit AChR antibodies. Surprisingly, these were partly directed at the main immunogenic region (MIR, thought to be alpha 67-76) and alpha-Bungarotoxin binding sites on rabbit AChR, and reacted less well with human AChR. Moreover, they could be separated from the anti-peptide antibodies by fractionation on immobilised peptide. We conclude that immunisation with these peptides led, by 'determinant spreading', to a response directed at self-AChR. Similar phenomena may have been overlooked in previous studies of responses to synthetic or recombinant AChR sequences. These findings suggest that autoimmunity could be induced by low-affinity, cross-reacting epitopes even when the observed serum response is highly specific for the autoantigen.

Animals↗
PubMed1994

Root surface texture after different scaling modalities.

Root surface texture after scaling with hand instruments, ultrasonic scalers (Amdent 830 and Cavi-Med 2000), and a sonic scaler (Titan-S) was assessed in vitro. The experimental material consisted of 48 extracted human teeth divided into six groups. Root surface texture was assessed with scanning electron microscopy (SEM). Hand and sonic instrumentation produced large grooves and removed cementum evident at a magnification of x 70, while the root surface alterations after ultrasonic instrumentation were not detectable below a magnification of x 500. The working principle of each scaling instrument in relation to its effect on the root surface was discussed.

Dental Cementum↗
PubMed1993

Detection of alpha-subunit isoforms in human muscle acetylcholine receptor by specific T cells from a myasthenia gravis patient.

The nicotinic acetylcholine receptor (AChR) is both the best-characterized transmitter receptor-ion channel and the target for the pathogenic antibodies in the human autoimmune disease myasthenia gravis (MG). In cloning and sequencing its components in man, we found that the alpha-subunit was transcribed in two isoforms, with (P3A+) or without (P3A-) a 75 base pair exon that had not been described in other species. While studying the human T lymphocyte response to recombinant AChR, we found that part of this P3A insert was recognized by one T cell line (from an MG patient), whereas another line only recognized the uninterrupted insertion site. To establish whether this exon is also translated in normal human muscle, we initially raised anti-peptide antibodies to the relevant amino acid sequences, but these failed to bind native AChR (affinity-purified from muscle on alpha-neurotoxin columns). We therefore exploited the great sensitivity and specificity of these T cells to detect the two isoforms after unfolding by antigen-presenting cells, and have been able to show that both are expressed in affinity-purified human muscle AChR.

Adult↗
PubMed1993

Corticosterone is a preferable ligand for measuring rat brain corticosteroid receptors: competition by RU 28362 and RU 26752 for dexamethasone binding in rat hippocampal cytosol.

It is unclear whether in vitro corticosteroid receptor binding assays have used inappropriately high concentrations of synthetic corticosteroid competitors, thereby potentially introducing error into estimates of type I (mineralocorticoid) and type II (glucocorticoid) receptor binding. To determine more accurately the concentration of blockers necessary to discriminate between these two sites, we have derived Ki values for the competition of dexamethasone, RU 28362 and RU 26752 for [3H]corticosterone and [3H]dexamethasone binding in rat hippocampus. Non-specific binding of both radioligands was defined with unlabeled dexamethasone to exclude transcortin. The type II agonist RU 28362 competed for only a portion of [3H]corticosterone binding, exhibiting a Ki of 0.5 nM for this binding. In contrast, RU 28362 fully competed all binding of a saturating concentration of [3H]dexamethasone, even though [3H]dexamethasone also recognized type I receptors, defined as specific [3H]corticosterone binding in the presence of 80 nM RU 28362. RU 28362 competition for [3H]dexamethasone binding exhibited characteristics of a 2-site interaction, with Kis of 0.3 and 194 nM. The type I receptor antagonist RU 26752 competed less effectively for [3H]corticosterone and [3H]dexamethasone binding, but nonetheless competed fully within a 1000-fold concentration range. Even at a level less than 125 x its Ki for type I binding, RU 26752 still inhibited virtually all type II receptor binding by [3H]corticosterone. We conclude that type I and II receptors in rat brain are best distinguished using [3H]corticosterone as the labelling ligand, with cold RU 28362 and dexamethasone to eliminate binding to type II and transcortin sites, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstanols↗
PubMed1993

Approaches for studying the pathogenic T cells in autoimmune patients.

Our provisional conclusions from this work are as follows. (1) For screening responses of established lines, native human AChR is not prohibitively scarce, especially if it is concentrated onto beads, and class II-transfected TE671 cells may be useful too; both may give vital evidence of AChR-specificity, but it is still crucial to confirm that with synthetic peptides. (2) For mapping epitopes, panels of full-length and shorter recombinant human polypeptides, and of synthetic peptides, are invaluable complementary material: longer peptides tend to stimulate particularly strongly. (3) Initial selection with pooled synthetic peptides can easily generate interesting lines from both patients and controls, but they may depend on the artificial processing sites that are an inevitable consequence of arbitrarily chosen start and stop points. Of course, these might conceivably be employed in unusual antigen-presenting cells (such as thymic myoid cells), so we cannot totally dismiss such "cryptic" epitopes. This system can sometimes select T cells responding to "natural" epitopes too, as now reported for tetanus toxin. Nevertheless, for these and other reasons, at present, we strongly favor using the longest human recombinant material possible, because it is apparently processed more naturally. This must be combined with rigorous screening for reactivity to E. coli-derived contaminants plus concomitant mapping of epitopes as above. Use of intact AChR for initiating lines may yet become feasible. (4) The T cells thus isolated and characterized so far are proving to be heterogeneous in the epitopes and presenting class II molecules they recognize, and in their T-cell receptor gene usage. It is premature to claim key myasthenogenic epitopes or clonotypes, but HLA-DR3 and the linked -DQw2 do not appear to monopolize presentation. (5) Assessing the disease-relevance of these T cells is a separate problem, highlighted by their apparent similarity in healthy controls. In the meantime, to test their potential pathogenicity, we are assaying their cytokine profiles and ability to help specific antibody production in vitro. In the hope that they do prove to be relevant, we are also using some of them to test possible therapeutic strategies that might prove applicable in the patients.

Amino Acid Sequence↗
PubMed1993

Perinatal factors associated with retinopathy of prematurity.

The etiology of retinopathy of prematurity appears to be multifactorial. Introduction of new treatments in neonatal care may add new risk factors. We have analyzed the relationship between 42 perinatal factors and the development of retinopathy of prematurity in 78 infants with a birth weight < 1501 g and/or gestational age < 33 weeks. We have also applied a chronological analysis of the maximum and minimum pO2 and pCO2 values. Retinopathy of prematurity was seen in 37 of 78 infants (47.4%). Nineteen factors were found to be related to the development of retinopathy of prematurity. However, when step-wise logistic regression analysis was used, only birth weight, number of days of oxygen therapy and use of beta-blocking agents by the mother before birth were found to be associated with the development of retinopathy of prematurity. The results suggest that medication with beta blockers immediately before birth should be used cautiously.

Blood Gas Analysis↗
PubMed1993

Visually impairing ROP in children born in Sweden 1975-89.

Among all children registered at the two educational resource centres in Sweden for visually impaired, we found 61 children with ROP causing their visual dysfunction, born 1975-89. Six children had a birthweight exceeding 1460 g, four of these were educationally blind. Sixty children had a gestational age of 30 weeks or less, one child had a gestational age of 31 weeks. Forty-one children had a visual acuity < or = 0.05 while 20 had visual acuity of 0.06-0.3 in the best eye. Twenty-four children had additional handicaps. Seven blind children had developed autistic features. Vitreoretinal surgery had been performed in 27 children. When the retina preoperatively was totally detached surgery failed to restore useful vision. We conclude that it is safer to define the risk group for ROP by gestational age than by birthweight. If the retina already is totally detached it seems advisable to refrain from vitreoretinal surgery.

Adolescent↗
PubMed1993

Epidemiology of ROP in the Stockholm area of Sweden.

A prospective, population-based study of the epidemiology of ROP in a well-defined geographical area of Sweden was performed. Two hundred and sixty children with a birth weight of 1500 g or less, and surviving for at least eight weeks, were included in the study. ROP was seen in 40.4% of the children. We suggest that prematurely born children with a gestational age of 32 weeks or less ought to be screened for ROP.

Cryosurgery↗
PubMed1993

A population based, prospective study of the development of ROP in prematurely born children in the Stockholm area of Sweden.

A prospective population based study including 260 children with a birth weight of 1500 g or less was performed in the Stockholm county. The total incidence of retinopathy of prematurity (ROP) was 40.4%, while severe ROP--that is, stage 3 or more, was seen in 20.0%. Cryotherapy was performed in 10.8%. Logistic regression analysis revealed independent association of both gestational age and birth weight with ROP. The association of gestational age and ROP was significantly stronger, indicating that the degree of immaturity of the eye is a main predictive factor for the development of ROP. The purpose of a general screening for ROP is to identify children requiring cryotherapy. Based on these results it seems appropriate to include children with a gestational age of 32 weeks or less in such a programme and a first examination at 5-6 weeks of postnatal age is suggested.

Birth Weight↗
PubMed1993

Augmented ACTH responses to stress in adrenalectomized rats replaced with constant, physiological levels of corticosterone are partially normalized by acute increases in corticosterone.

Adrenalectomized rats replaced with constant, physiological levels of corticosterone via a subcutaneous pellet (Pellet) have normal basal morning ACTH but exhibit enhanced and prolonged ACTH responses to stress vs. sham-operated (Sham) rats. It has not been determined if the lack of either stress-induced or circadian increases in corticosterone, both of which are missing in Pellet rats, may account for this enhanced response. To test the extent to which stress-associated increases in corticosterone alone can normalize stress-induced hypersecretion of ACTH, we approximated endogenous secretion by injecting additional corticosterone in Pellet rats via an indwelling subcutaneous cannula, 5 min before hypoxia stress (10% O2). A corticosterone dose of 666 micrograms/kg (Pellet+B), but not 333 micrograms/kg (Pellet+Low B), produced plasma corticosterone levels comparable to those in Shams and normalized stress-induced but not post-stress plasma ACTH. Administration of the type II corticosteroid receptor antagonist RU 38486 30 min before corticosterone reversed this inhibition. We conclude that enhanced ACTH responses to stress in Pellet rats result in large part from lack of type II receptor-mediated feedback inhibition by corticosterone increases during stress, although prior circadian increases in corticosterone may also be required.

Adrenalectomy↗
PubMed1993

Bridging the nursing research-practice gap through research utilization.

This article explores the gap that currently exists between nursing research and nursing practice. The aim is to promote the conversion of new knowledge into practical innovations. Barriers to research utilization in practice settings come from both the academic and clinical arenas. Innovative models and strategies are needed to overcome these barriers. The purposes and value of research utilization and the clinical and academic strategies that facilitate research are discussed. Supporting clinical studies are provided as exemplars.

Clinical Nursing Research↗
PubMed1993

A century of progress: nursing quality improvement at the Mount Sinai Medical Center.

Since The Mount Sinai Hospital in New York City began delivering care in the mid 1800s, the medical services and, shortly thereafter, the nursing service have consistently given priority to improving patient care. Through the decades of the late 19th and 20th centuries, the Department of Nursing has remained current with the evolving concept of quality improvement. A historical overview of key elements in the evolution of quality improvement in nursing is presented.

Hospital Units↗