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Biomedical subjects

S A Hoffman

Publications and source records attributed to S A Hoffman.

At least 19 recordsLinked to original sources
PubMed1995

Characterization of murine brain-reactive monoclonal IgG autoantibodies.

A diversity of brain-reactive autoantibodies (BRAA) is found in the sera and cerebrospinal fluid in elevated amounts in systemic lupus erythematosus (SLE) and correlates with some CNS manifestations of both human and murine SLE. In order to test the hypothesis that BRAA mediate the CNA manifestations, we are developing a library of brain-reactive monoclonal autoantibodies (BRMA) from autoimmune mice for characterization. We have recently reported on the production of BRMA of the IgM class from unimmunized autoimmune mice. In the current study we extend our investigations and report on the production and characterization of two BRMA of the IgG class. These antibodies react against integral brain membrane antigens of approximately 58, 32, and 30 kDa by immunoblot. Reactivity to such antigens is also found in a majority of the autoimmune murine serum samples tested, but not in nonautoimmune mice. These IgG BRMA show reactivity to cell bodies of the cerebral cortex, hippocampus, and hypothalamus of murine brain but not to fiber tracts. They also react with an integral thymus membrane antigen, but not to antigens of other tissues tested. Because of their properties, BRMA such as those characterized here are likely to be of pathogenic significance in CNS involvement in SLE.

Animals↗
PubMed1994

Nanometer spatial resolution achieved in hard x-ray imaging and Laue diffraction experiments.

Tapered glass capillaries have successfully condensed hard x-ray beams to ultrasmall dimensions providing unprecedented spatial resolution for the characterization of materials. A spatial resolution of 50 nanometers was obtained while imaging a lithographically prepared gold pattern with x-rays in the energy range of 5 to 8 kiloelectron volts. This is the highest resolution scanning x-ray image made to date with hard x-rays. With a beam 360 nanometers in diameter, Laue diffraction was observed from the smallest sample volume ever probed by x-ray diffraction, 5 x 10(-3) cubic micrometers.

Crystallography, X-Ray↗
PubMed1993

Effects of peripheral cytokine injections on multiple unit activity in the anterior hypothalamic area of the mouse.

The brain and the immune system interact in a bidirectional manner. This study on neuroimmune circuitry investigated the hypothesis that circulating cytokines act as messengers in the communication from the immune system to the brain and that the anterior hypothalamus is an integral part of this pathway. It was predicted that, following tail vein injections in mice, the cytokines interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), and interleukin-6 (IL-6) would alter electrical activity in the anterior hypothalamus. Differential electrodes were used to record multiple unit activity, at 5-min intervals, immediately before and for 60 min following injections. IL-1 beta and IL-2 decreased activity in the lateral margin of the anterior hypothalamus. IL-2-responsive neurons seemed to be localized to this area, while IL-1 beta-sensitive neurons showed a larger area of distribution. A significant response following IL-6 administration was not demonstrated. The observed changes in electrical activity support the concept of the hypothalamus as a sensory integration site for the immune system. Alternative models for the mechanism of cytokine signaling are discussed.

Action Potentials↗
PubMed1993

Brain reactive monoclonal auto-antibodies: production and characterization.

To determine the role of auto-antibodies in the pathogenesis of neuropsychiatric manifestations of systemic lupus erythematosus (NP-SLE), it will be necessary to characterize the diversity of auto-antibodies that exist. This can be done by producing a library of monoclonal, brain-reactive auto-antibodies. From such a library the antigens to which the antibodies bind, and whether there are any interesting relations between these antigens, can be determined. Behavioral effects can also be investigated. Toward these ends, brain-reactive monoclonal auto-antibodies (BRMA) were produced. The production and characterization of two monoclonal antibodies is presented in this study.

Animals↗
PubMed1993

Anti-brain antibodies in the sera of rheumatoid arthritis patients: relation to disease activity and psychological status.

Auto-antibodies reactive with brain are known to occur in various immunological disorders. Their significance with respect to disease activity, neurological manifestations, or psychological status is, however, not known. In previous studies it was found that there were antibodies reactive with brain in the sera of patients with rheumatoid arthritis (RA). The present study sought to confirm and extend our previous findings and determine the significance of these antibodies with respect to disease activity. It also investigated a possible connection between psychological function in RA and these auto-antibodies. Sera drawn from 14 RA patients, at bi-weekly intervals over 3 months, showed the presence of antibodies against transmembrane proteins from murine brain. These antibodies correlated positively with rheumatoid factor and joint swelling. There was a trend toward a correlation between depression and daily mood scores and the number of antibodies reactive with brain. In addition, a correlation between cognitive coping styles in RA patients and auto-antibodies was found. There was also evidence for a sub-population of pathogenic antibodies.

Adaptation, Psychological↗
PubMed1992

Detection of brain-reactive autoantibodies in the sera of autoimmune mice using ELISA.

There are considerable problems with developing an assay to detect the often small quantities of autoantibodies which react against antigens in a heterogeneous and complex mixture from a source such as brain. An indirect enzyme-linked immunosorbent assay (ELISA) has been developed which can detect naturally occurring autoantibodies in serum that are reactive with integral brain membrane antigens. Sera were collected from autoimmune BXSB and NZB mice and non-autoimmune C57BL/6 mice at various ages and were assayed for the presence of brain-reactive autoantibodies (BRAAs). It is shown that this technique provides a highly sensitive, specific, and rapid assay for detecting BRAAs in serum. It shows that integral membrane antigens from whole brain can be isolated and used to detect and quantitate antibodies in the sera of autoimmune and non-autoimmune mice. The data also confirm studies, using different techniques, showing higher levels of autoantibodies to brain in autoimmune as compared to non-autoimmune mice. There are numerous potential applications for this ELISA, such as in rapidly screening large numbers of samples of biological fluids, tracking autoimmune disease progression over time, detecting small quantities of antibody against brain antigens, and as an assay system for investigating the role of BRAAs in the pathogenesis of immune mediated CNS disease.

Animals↗
PubMed1990

Brain specific autoantibodies in murine models of systemic lupus erythematosus.

Autoantibodies which bind to integral membrane proteins of brain were tested for their ability to bind to cross-reactive antigens on non-neural tissue. Both brain specific autoantibodies and antibodies which bind to cross-reactive antigens were found. There were two types of brain reactive autoantibodies which could not be adsorbed by non-neural tissue. One type was adsorbable by crude cell membrane preparations of brain. The second type was reactive against integral membrane proteins of brain, but not adsorbable by any of the crude membrane preparations tested. Autoantibodies of the first type reacted against integral membrane proteins with apparent molecular weights of 75, 70, 62, 50, 27, 24 and 20 kDa, as determined by gel electrophoresis and immunoblotting. As in previous studies, a diversity of brain reactive autoantibodies were found. The greatest numbers and strongest banding patterns were seen in the autoimmune strains of mice. The non-autoimmune strain displayed these autoantibodies at much lower levels. These results are the first to find brain specific autoantibodies, from autoimmune mice, against integral brain membrane antigens. The data support the idea that there is a sub-population of brain reactive autoantibodies which are involved in the pathogenesis of neuropsychiatric manifestations in immunologic disorders, particularly systemic lupus erythematosus.

Animals↗
PubMed1989

Characterization of brain-reactive autoantibodies in murine models of systemic lupus erythematosus.

Using the Western blot technique we analyzed the sera of five strains of mice that develop a disease like systemic lupus erythematosus (SLE), along with two normal strains, for their binding specificities against isolated mouse integral brain membrane proteins. This report describes the distribution and frequency of the more than 200 brain-reactive autoantibodies in the 126 animals tested and verifies the hypothesis of diversity in anti-brain antibodies produced during autoimmune conditions such as SLE. These results emphasize the importance of characterizing the brain-reactive autoantibodies in the sera or cerebrospinal fluid of SLE patients with central nervous system involvement.

Animals↗
PubMed1988

Identification of autoantibody reactive integral brain membrane antigens. A two-dimensional analysis.

A procedure to identify murine autoantibody reactive, integral membrane antigens of brain is described. This involved the isolation of integral membrane antigens from whole brain followed by two-dimensional (2D) gel electrophoretic separation and transfer to nitrocellulose (NC) membrane. A 2D 'map' was then constructed by an effective total protein staining procedure. This 'map' was subsequently compared with similar blots that were reacted with autoimmune sera, stained for immunoglobulin and the reactive antigens identified. Advantages of this procedure include economy in the reagents and sera used, not having to use radioactive substances and much shorter working time. This technique will permit the identification of brain reactive autoantibodies.

Animals↗
PubMed1988

Characterization of cell surface antigens on the adrenergic neuroblastoma clone A2(1).

Neuroblastoma cell lines have been extensively used to identify the presence of brain reactive autoantibodies in the sera of patients with systemic lupus erythematosus (SLE) who have neuropsychiatric involvement and in the animal models (murine) of this disorder. In this study, a characterization of murine neuroblastoma cell surface antigens, from the adrenergic A2(1) cell line, have indicated both similarities and differences with the cell surface antigens of normal mouse brain. It has also shown that some of these antigens are nervous system specific, whereas others are not. These data indicate that a more precise definition of the antigens on the surface of neuroblastoma cells, with which anti-brain autoantibodies react, is necessary for an understanding of the neuropsychiatric manifestations associated with autoimmune diseases such as SLE.

Adrenergic Fibers↗
PubMed1987

Brain-reactive autoantibody levels in the sera of ageing autoimmune mice.

Brain-reactive autoantibodies are thought to play an important role in mediating central nervous system (CNS) disorders in systemic lupus erythematosus (SLE). In this paper the developmental occurrence of these antibodies in the sera of autoimmune mice, i.e. NZB, NZB/W, MRL/l and BXSB mice were examined. All murine strains tested, whether autoimmune or not, showed some degree of serum reactivity toward brain antigens. Autoimmune mice, however, displayed higher levels of serum brain-reactive antibodies, and at earlier ages, than non-autoimmune mice. Immunofluorescence assays against brain sections and adsorption assays, with both neural and non-neural tissue, indicated a heterogeneity in the specificity of the populations of brain-reactive antibodies present. These studies provide an important step in characterizing the appearance and diversity of brain-reactive autoantibodies, with the goal of better understanding their significance and potential role in mediating CNS dysfunction in SLE.

Aging↗
PubMed1987

Dream bizarreness and the activation-synthesis hypothesis.

The unusual aspect of dream consciousness which has been called "dream bizarreness" may be defined as impossibility or improbability in the domains of dream plot, cognition and affect. The bizarre features of dreams may be divided into three broad categories: discontinuities, incongruities and uncertainties. Discontinuities are interruptions in orientational stability; incongruities are inappropriate syntheses of mismatching plot elements; uncertainties are confusions of distinct conceptions. Dream bizarreness appears to be the manifestation of some state-dependent cognitive process which is probably rooted in REM sleep neurophysiology. In the waking state, our brain/minds are capable of remaining focused on the normal flow of ongoing information, and such features of life as plot and time unfold in a linear sequence. In REM sleep/dreaming, this function appears to be interfered with, and disparate elements of consciousness are suddenly interjected as the brain/mind cannot maintain its orientational focus in the usual way.

Arousal↗
PubMed1983

Permeability of the blood cerebrospinal fluid barrier during acute immune complex disease.

Changes in the permeability of the blood-brain barrier (BBB) and blood-cerebrospinal fluid (blood-CSF) barrier in rabbits were assessed by using a sensitive double isotope technique at different times after the induction of acute immune complex disease (AICD). Induction of AICD was done with a single large dose of bovine serum albumin, whereas controls received only saline. Animals were sacrificed 6, 9, 12, 15, and 18 days after induction. Extravasation of protein was measured by injecting rabbits i.v. with 131I-rabbit serum albumin (RSA) 24 hr before sacrifice. In order to correct for intravascular blood volume, 125I-RSA was injected 5 min before sacrifice. Extravascular blood equivalents (EVBE), a measure of barrier permeability, were elevated in the CSF of rabbits sacrificed on days 12 and 15. None of the brain regions from any of the animal groups showed any changes or significant differences from controls in EVBE values on these days. These results indicate that there was an increase in the permeability of the blood-CSF barrier to radiolabeled albumin but not in the BBB proper during the time that CSF IgG levels were elevated in AICD. The potential significance of these findings for the mechanisms mediating central nervous system involvement in systemic lupus erythematosus is discussed.

Acute Disease↗
PubMed1982

Suppression of water intake by immune complex formation in the hypothalamus. Implications for systemic lupus erythematosus.

Immune complex formation in the perifornical region of the hypothalamus resulted in depressed water consumption in rats, but did not consistently alter body temperature. The antibody with an unrelated antigen did not affect water consumption or body temperature. These results support the notion that immune complex reactions within the central nervous system can alter behavior.

Animals↗
PubMed1982

Prostatic acid phosphatase and sperm in the post-coital vagina.

Sperm and prostatic acid phosphatase identified in vaginal fluid after an alleged sexual assault constitute important physical evidence useful in courts of law during rape trials. The purpose of this study was to define a normal and abnormal range for acid phosphatase in the post-coital vagina for our emergency department and to compare the sensitivity of acid phosphatase versus sperm in determining recent coitus. Vaginal swabs obtained from 90 patients were analyzed for acid phosphatase activity by the Sigma p-nitrophenyl phosphate technique. Swabs were stored in a bovine albumin preservative broth. Pap smears for sperm identification were also performed. Acid phosphatase values greater than 50, especially those greater than 138 Sigma units/cc, correlated with intercourse within the preceding 24 hours (P .005). Values greater than 20 but less than 50 correlated with intercourse within 48 hours (P .005). The presence or absence of sperm was found to be less sensitive, and correlated poorly with the time since intercourse [of 12 cases less than or equal to 24 hours, 11 were acid phosphatase-positive (91.7%) while seven were sperm-positive (58.4%)].

Acid Phosphatase↗