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Biomedical subjects

E M Eisenstein

Publications and source records attributed to E M Eisenstein.

At least 19 recordsLinked to original sources
PubMed2006

A behavioral homeostasis theory of habituation and sensitization: II. Further developments and predictions.

Habituation may be viewed as a decremental behavioral change to iterative stimuli of little immediate relevance. It is observed from protozoa to humans, indicating its evolutionary significance. If habituation is interpreted as the process of filtering out unimportant repetitive stimuli, then how should sensitization be interpreted? The 'behavioral homeostasis theory' of these two behaviors is based on the notion that organisms at a high level of 'alertness' prior to experiencing a new iterative stimulus will show a large initial response followed by a decrement (habituation) if the stimulus is of little significance. Conversely, the same organism at a low level of 'alertness' will show a small initial response to the same stimulus followed by an increase in 'alertness' and a larger response to the next stimulus (sensitization) in order to receive enough information to assess its significance. Circadian rhythmicity is hypothesized to play a role in determining 'alertness' to a new iterative stimulus at any given time. The level of responsiveness in initial habituaters and sensitizers, as an asymptote is approached, is a balance between being too 'alert' to an unimportant stimulus and missing other significant stimuli, and being too 'un-alert' and missing a change in the relevance of the present iterative stimulus. The concept of 'behavioral homeostasis' includes behaviors beyond habituation and sensitization across phylogeny. It includes instinctive as well as learned, and group as well as individual behavior. Such behavioral homeostatic processes to optimize detection and assessment of constantly occurring external stimuli are critical for organism survival. Clinical implications of this theory are also examined.

Animals↗
PubMed2002

Acute rheumatic fever associated with Henoch-Schönlein purpura: report of three cases and review of the literature.

AIM: To describe a possible relationship between Henoch-Schönlein purpura and rheumatic fever. METHODS: Patients with features of both diseases were identified by reviewing the hospital records. Medline and reference lists from published articles were used to search for previous reports of the two conditions occuring simultaneously. RESULTS: Three newly described cases, and three previous reports of Henoch-Schönlein purpura associated with rheumatic carditis or chorea were identified. CONCLUSIONS: The coexistence of these two disorders in some patients supports the view that Group A streptococcus may have a pathogenic role in Henoch-Schönlein purpura.

Acute Disease↗
PubMed1999

Transfer of learned information between ganglia in the insect ventral nerve cord.

A yoked control training procedure was used on the decapitated cockroach, L. maderae. The right prothoracic leg was trained to lift in order to avoid a shock. It was found that this information transferred via the two interganglionic connectives from the first or prothoracic ganglion (T1) to the second or mesothoracic ganglion (T2) so that now the right mesothoracic leg lifted to avoid shock even though it was not directly trained. If both connectives were cut before training T1, no transfer to T2 was seen, i.e. the mesothoracic leg did not lift and avoid shock. However, if both connectives were cut immediately after training T1, the information had already transferred and was available for use by T2. There was redundancy in the transfer in that either connective alone could carry the same information from T1 to T2. Either mesothoracic leg could tap into this information. Using a reversible cold block on the connectives, it was found that if it was applied before training T1 it did not interfere with T1 learning but no transfer to T2 was seen after the cold block wore off. That the block was transitory and did not permanently impair the connectives was shown by the fact that if it was applied and then allowed to wear off before training began there was normal learning in T1 and transfer to T2. The transection and cold-block studies were consistent in demonstrating that the transfer of the information was 'on-line' and only occurred during T1 learning. If transfer was blocked during T1 learning the information could not be transferred or tapped into by T2 at a later time even though it was stored in T1 and available for later use by T1. The transfer occurred so quickly it most likely occurred via nerve impulses. Because no primary sensory or motor neurons are in the connectives, the information must have been coded onto interneurones for transfer from the first (T1) to the second (T2) ganglion.

Animals↗
PubMed1997

A comparative approach to the behavior called "learned helplessness'.

The phenomenon of 'learned helplessness' is seen broadly across the animal kingdom. The basic characteristics of this behavior are similar in intact mammals, lower vertebrates and invertebrates. In fact, the basic characteristics even are seen in an isolated thoracic ganglion of an insect. The brain is evidently not essential either in mammals or in invertebrates for demonstrating this behavior. A neutral terminology is suggested that allows for investigation of this behavior and its underlying mechanisms in both intact and surgically simplified preparations of both vertebrates and invertebrates. Thus, its phylogeny can be investigated. In addition, simpler systems such as the insect ventral nerve cord with its large neurons and its ease of pharmacological manipulation may have important contributions to make to understanding the neuropharmacology underlying it. The ubiquity of the phenomenon in different phyla suggests that while in the laboratory it may appear maladaptive, this may not necessarily be the case in a natural ecological context. Because of increasing governmental regulations in both Europe and the US on mammalian studies involving shock and distress, such as that associated with 'learned helplessness', it may be prudent to consider other systems that may offer insight into its underlying mechanisms.

Adaptation, Psychological↗
PubMed1997

Selecting a model system for neurobiological studies of learning and memory.

This article discusses the logic underlying the use of invertebrate model systems for investigating the neurobiological basis of learning and memory, the kinds of questions which can be asked of these systems as well as their limitations. A model system selected to answer specific questions about learning and memory is most useful if its selection is based on strategy rather than chance.

Animals↗
PubMed1996

Magnetic resonance imaging (MRI) detection of the murine brain response to light: temporal differentiation and negative functional MRI changes.

Using a 9.4 T MRI instrument, we have obtained images of the mouse brain response to photic stimulation during a period between deep anesthesia and the early stages of arousal. The large image enhancements we observe (often >30%) are consistent with literature results extrapolated to 9.4 T. However, there are also two unusual aspects to our findings. (i) The visual area of the brain responds only to changes in stimulus intensity, suggesting that we directly detect operations of the M visual system pathway. Such a channel has been observed in mice by invasive electrophysiology, and described in detail for primates. (ii) Along with the typical positive response in the area of the occipital portion of the brain containing the visual cortex, another area displays decreased signal intensity upon stimulation.

Animals↗
PubMed1995

Habituation of the galvanic skin response to tone as a function of age.

Habituation of the galvanic skin response (GSR) to tone in male college students varying in age from 18-39 years old was examined. Older subjects habituated more slowly to tone than did younger ones. This confirmed our past work on habituation of the GSR to electric shock. The GSR is shown to be a sensitive and reliable measure of small differences in age as it affects learning. The clinical usefulness of this quantitative and sensitive measure in detecting small and early changes in learning and memory deficits associated with age and dementia is discussed.

Acoustic Stimulation↗
PubMed1994

B cell differentiation defects in common variable immunodeficiency are ameliorated after stimulation with anti-CD40 antibody and IL-10.

In these studies we show that although purified B cells of patients with common variable immunodeficiency (CVI) have a normal capacity to proliferate, they manifest differentiation defects at multiple levels. Compared with controls, circulating CVI B cell populations contain reduced numbers of sIgG+ and sIgA+ cells with a commensurate increase in sIgM+ B cells, suggesting an in vivo defect in isotype switch. In addition, CVI B cells manifest Ig secretion defects on stimulation with either anti-CD40 and IL-10 or SAC and IL-2 and IL-10, which are of increasing severity for IgM, IgG, and IgA, respectively. These Ig secretion defects are not overcome by addition of a variety of cytokines, including TGF-beta, to anti-CD40-driven cultures. In further studies we show that despite the above abnormalities, CVI B cells are induced to express normal or near-normal levels of C mu, C gamma, and C alpha mRNA after 7 days of stimulation with anti-CD40 and IL-10. That this CH mRNA expression represents a recovery of CVI B cell differentiation is supported by studies of Ig secretion in which CVI B cells that are first stimulated for 7 days with anti-CD40 and IL-10 and then restimulated in coculture with activated normal allogeneic T cells and IL-10, secrete substantial levels of IgM and IgG and increased amounts of IgA. Overall, therefore, CVI B cell function can be significantly improved by maintenance in culture. These data suggest the abnormalities of B cell differentiation in CVI are reversible and that the defect is a form of B cell anergy.

Adult↗
PubMed1994

Treatment of refractory disseminated nontuberculous mycobacterial infection with interferon gamma. A preliminary report.

BACKGROUND: Studies conducted in vitro and in animals suggest that cytokine signals to monocytes or macrophages by interferon gamma are important in the containment and clearance of disseminated nontuberculous mycobacterial infections. METHODS: We studied seven patients with refractory, disseminated nontuberculous mycobacterial infections who were not infected with the human immunodeficiency virus. Three patients were from a family predisposed to the development of Mycobacterium avium complex infections; four patients had idiopathic CD4+ T-lymphocytopenia. Their infections were culture- or biopsy-proved, involved at least two organ systems, and had been treated with the maximal tolerated medical therapy. Cellular proliferation, cytokine production, and phagocyte function were assessed in peripheral-blood cells. Interferon gamma was administered subcutaneously two or three times weekly in a dose of 25 to 50 micrograms per square meter of body-surface area in addition to antimycobacterial medications. Clinical effects were monitored by cultures, biopsies, radiographs, and in one patient a change in the need for paracentesis. RESULTS: In response to phytohemagglutinin, the production of interferon gamma by mononuclear cells from the patients was lower than in normal subjects (P < 0.001), whereas stimulation with ionomycin and phorbol myristate acetate led to normal production of interferon gamma in the patients. Within eight weeks of the start of interferon gamma therapy, all seven patients had marked clinical improvement, with abatement of fever, clearing of many lesions and quiescence of others, radiographic improvement, and a reduction in the need for paracentesis. CONCLUSIONS: Interferon gamma in combination with conventional therapy may be effective for some cases of refractory disseminated nontuberculous mycobacterial infection.

Adult↗
PubMed1994

A unique syndrome of immunodeficiency and autoimmunity associated with absent T cell CD2 expression.

CD2 is a glycoprotein expressed on the surface of human T cells that mediates adhesion between T cells and antigen presenting cells. CD2 also functions in concert with the T cell receptor to transduce signals that lead to T cell activation. The CD8 and CD4 molecules are transmembrane glycoproteins that are expressed on mutually exclusive populations of mature T cells and bind to determinants on major histocompatibility complex class I and class II molecules respectively. Like CD2, CD4 and CD8 function to promote adhesion between T cells and antigen presenting cells and potentiate signaling via the T cell receptor. We studied a patient with idiopathic lymphopenia and disseminated infection with Mycobacterium avium. The patient also suffered from recurrent deep venous thrombosis in association with anticardiolipin and anti-DNA antibodies. Peripheral blood T cells from this patient were polyclonal and expressed no detectable CD2 RNA or protein as determined by northern blotting, immunofluorescent staining with anti-CD2 antibodies, and failure to form rosettes with sheep red blood cells. In addition, the majority (85%) of this patient's T cells did not express either CD4 or CD8 but did express the alpha/beta T cell receptor. T cells from this patient failed to respond to stimulation with alloantigen or specific antigen. In contrast, there was a normal response to stimulation with immobilized anti-CD3 antibody. The clinical and immunologic findings in this patient provide in vivo evidence that the accessory molecules CD2, CD4, and CD8 play important roles in the regulation of normal human T cell activation.

Antigens, Surface↗
PubMed1994

Leg position learning in the cockroach nerve cord using an analog technique.

The ultimate goal of this research is to correlate neural activity with leg behavior during learning. Contrary to previous studies of shock avoidance learning in the headless cockroach, in which an all-or-none method of recording was used, we have adopted a direct analog recording of leg position to measure learning in the prothoracic ganglion. This method provides a sensitive and continuous record of leg movement that can be correlated with the interactions of individual neurons that may be involved in such learning. Of the 10 prothoracic legs trained to flex to avoid shock, eight escaped shock by flexion within a maximum of 13 min and seven showed savings when retested. Only four of eight prothoracic legs trained to extend showed avoidance learning and all four showed savings. Electrical stimulation of nerves 3,4,5, and 6 innervating the prothoracic leg revealed which nerves were instrumental in the flexion and extension responses.

Animals↗
PubMed1994

Common variable immunodeficiency: diagnosis and management.

OBJECTIVE: Common variable immunodeficiency is a heterogeneous syndrome characterized by humoral immunodeficiency, recurrent bacterial infections, and a variety of immunologic abnormalities. The goal of this article is to review the pathogenesis, clinical manifestations, diagnosis, and management of common variable immunodeficiency. DATA SOURCES: References are limited to the English language literature. Sources include computerized databases and bibliographies of recent articles and books. STUDY SELECTION: References that made important contributions to our understanding of the pathogenesis, clinical manifestations, diagnosis, and treatment of this disease were selected for inclusion in this review. RESULTS AND CONCLUSION: Common variable immunodeficiency is an idiopathic state of immune dysregulation that results in impaired antibody synthesis and the development of recurrent bacterial infections. This syndrome is also associated with a variety of autoimmune and neoplastic disorders. Effective management of these patients includes intravenous immunoglobulin replacement, vigorous treatment of infections, and readiness to promptly evaluate and treat unusual autoimmune and neoplastic complications should they appear.

Common Variable Immunodeficiency↗
PubMed1993

Reduced interleukin-2 (IL-2) production in common variable immunodeficiency is due to a primary abnormality of CD4+ T cell differentiation.

Common variable immunodeficiency (CVI) is a condition characterized by hypogammaglobulinemia and impaired antibody responses, resulting in recurrent bacterial infections in untreated patients. In addition, affected individuals exhibit an increased incidence of autoimmunity, malignancy, and certain viral infections, suggesting the presence of an underlying generalized immune dysregulation. We have previously described a subgroup of CVI patients in whom T cells within PBMC populations exhibit a selective defect in lymphokine production. IL-2, IL-4, and IL-5 mRNA production was impaired in these patients, while proliferation, IL-2R expression, and c-myc mRNA production were normal. In the present series of experiments, using highly purified CD4+ T cells prepared by negative selection, we show that this lymphokine production defect is a primary abnormality of CVI CD4+ T cells: whereas CD4+ T cells from CVI patients proliferate normally in response to stimulation by PHA, staphylococcal enterotoxin B (SEB), or anti-CD2 antibodies, these stimuli induce significantly less IL-2 production than observed with CD4+ T cells from normal individuals. Furthermore, we show that this IL-2 production defect is not due to an accessory cell abnormality, since it was seen in the presence of normal (allogeneic) accessory cells, and patient accessory cells supported normal amounts of IL-2 production by PHA-stimulated CD4+ T cells obtained from normal individuals. Of interest, we also found that while IL-2 production by CD4+ T cells from CVI patients induced by stimulation with immobilized anti-CD3 antibody was reduced compared to CD4+ T cells from normal control individuals, this reduction was not statistically significant. Furthermore, stimulation of both CVI patient and normal CD4+ T cells with either ionomycin+phorbol myristate acetate or a combination of immobilized anti-CD3 antibody plus anti-CD28 antibody resulted in a 50-fold increase in IL-2 production compared to stimulation with immobilized anti-CD3 antibody alone, and, under these conditions, CVI and normal CD4+ T cells produced equivalent amounts of IL-2. Finally, minor defects in interferon-gamma production by CD4+ T cells from CVI donors were observed, but these were less severe than the IL-2 production defects and were not statistically significant. We conclude that a primary abnormality of lymphokine production exists in the CD4+ T cells of a subset of patients with CVI.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1993

An analog technique for recording leg position learning in the cockroach.

Past studies of shock avoidance learning in the cockroach have used an all-or-none method of recording leg position. Leg position was recorded indirectly in terms of the number of shocks the leg initiated. The measure of learning was the decrease in the number of times the leg initiated shock. An analog procedure is described that allows the pattern of leg behavior change to be assessed directly. Thus, the time course and relative magnitude of leg flexions and extensions prior to, during, and following shock can be studied. It will be possible to record peripheral motor nerve activity simultaneously with the behavior and to examine the excitatory and inhibitory interactions of individual neurons that may be involved in such learning.

Animals↗