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L Jacobson

Publications and source records attributed to L Jacobson.

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

AIDS--mémoire.

A czar was born when President Clinton named Kristine M. Gebbie to be his national AIDS policy coordinator. But a year later, under unrelenting fire from AIDS activists, Gebbie resigned. Her departure underscores the trouble that some activists have had shifting from the outsider's game to the insider's.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Long-term problem.

Explore the source record for details and available documents.

Health Care Costs↗
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↗
PubMed1994

Replication of a high-probability request sequence with varied interprompt times in a preschool setting.

An intervention for noncompliance consisting of a series of requests promoting a high probability of compliance followed either 5 s or 20 s later by a request with a low probability of compliance was implemented with a preschool child with autism. Results indicated that applications of the request sequence with a shorter interprompt time resulted in higher rates of compliance, and longer interprompt times resulted in near-baseline rates of compliance.

Journal Article↗
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↗