Showing papers by "Stony Brook University published in 1993"
TL;DR: Data support the involvement of ApoE ϵ4 in the pathogenesis of late-onset familial and sporadic AD and suggest it may operate as a susceptibility gene (risk factor) for the clinical expression of AD.
Abstract: Apolipoprotein E, type epsilon 4 allele (APOE epsilon 4), is associated with late-onset familial Alzheimer's disease (AD). There is high avidity and specific binding of amyloid beta-peptide with the protein ApoE. To test the hypothesis that late-onset familial AD may represent the clustering of sporadic AD in families large enough to be studied, we extended the analyses of APOE alleles to several series of sporadic AD patients. APOE epsilon 4 is significantly associated with a series of probable sporadic AD patients (0.36 +/- 0.042, AD, versus 0.16 +/- 0.027, controls [allele frequency estimate +/- standard error], p = 0.00031). Spouse controls did not differ from CEPH grandparent controls from the Centre d'Etude du Polymorphisme Humain (CEPH) or from literature controls. A large combined series of autopsy-documented sporadic AD patients also demonstrated highly significant association with the APOE epsilon 4 allele (0.40 +/- 0.026, p < or = 0.00001). These data support the involvement of ApoE epsilon 4 in the pathogenesis of late-onset familial and sporadic AD. ApoE isoforms may play an important role in the metabolism of beta-peptide, and APOE epsilon 4 may operate as a susceptibility gene (risk factor) for the clinical expression of AD.
3,551 citations
01 Jan 1993
2,171 citations
TL;DR: In an autopsy series of brains of late-onset AD patients, a strong association of APOE4 allele with increased vascular and plaque A beta deposits is found.
Abstract: Amyloid beta-peptide (A beta) deposition in senile plaques and cerebral vessels is a neuropathological feature of Alzheimer disease (AD). We examined the possibility that commonly observed variability in A beta deposition in late-onset AD might be related to apolipoprotein E genotype (APOE gene; the two most common alleles are 3 and 4), since APOE4 is a susceptibility gene for late-onset AD and apolipoprotein E interacts strongly with A beta in vitro. In an autopsy series of brains of late-onset AD patients, we found a strong association of APOE4 allele with increased vascular and plaque A beta deposits. Late-onset AD patients with one or two APOE4 alleles have a distinct neuropathological phenotype compared with patients homozygous for APOE3.
1,468 citations
TL;DR: In this article, a rating scale was designed to measure dysfunctional discipline practices in parents of young children and three stable factors of dysfunctional discipline style were identified: (a) Laxness, (b) Overreactivity, and (c) Verbosity.
Abstract: A rating scale was designed to measure dysfunctional discipline practices in parents of young children. Three stable factors of dysfunctional discipline style were identified: (a) Laxness, (b) Overreactivity, and (c) Verbosity. The Parenting Scale exhibited adequate internal consistency and test–retest reliability. Mothers of clinic children reported more dysfunctional parenting than did mothers of nonclinic children. Parenting Scale scores were related to maternal ratings of child behavior and marital discord. Most important, Parenting Scale scores correlated significantly with observational measures of dysfunctional discipline and child misbehavior.
1,392 citations
TL;DR: Differences in the two isoforms in complexing with the beta/A4 peptide may be involved in the pathogenesis of the intra- and extracellular lesions of Alzheimer disease.
Abstract: Apolipoprotein E (apoE), a plasma apolipoprotein that plays a central role in lipoprotein metabolism, is localized in the senile plaques, congophilic angiopathy, and neurofibrillary tangles of Alzheimer disease. Late-onset familial and sporadic Alzheimer disease patients have an increased frequency of one of the three common apoE alleles, epsilon 4, suggesting apoE4 is associated with increased susceptibility to disease. To follow up on this suggestion, we compared the binding of synthetic amyloid beta (beta/A4) peptide to purified apoE4 and apoE3, the most common isoform. Both isoforms bound synthetic beta/A4 peptide, the primary constituent of the plaque and angiopathy, forming a complex that resisted dissociation by boiling in SDS. Oxygen-mediated complex formation was implicated because binding was increased in oxygenated buffer, reduced in nitrogen-purged buffer, and prevented by reduction with dithiothreitol or 2-mercaptoethanol. Binding of beta/A4 peptide was saturable at 10(-4) M peptide and required residues 12-28. Examination of apoE fragments revealed that residues 244-272 are critical for complex formation. Both oxidized apoE4 and apoE3 bound beta/A4 peptide; however, binding to apoE4 was observed in minutes, whereas binding to apoE3 required hours. In addition, apoE4 did not bind beta/A4 peptide at pH < 6.6, whereas apoE3 bound beta/A4 peptide from pH 7.6 to 4.6. Together these results indicate differences in the two isoforms in complexing with the beta/A4 peptide. Binding of beta/A4 peptide by oxidized apoE may determine the sequestration or targeting of either apoE or beta/A4 peptide, and isoform-specific differences in apoE binding or oxidation may be involved in the pathogenesis of the intra- and extracellular lesions of Alzheimer disease.
1,364 citations
TL;DR: When compared to normal controls, cocaine abusers showed significant decreases in dopamine D2 receptor availability which persisted 3‐4 months after detoxification, and these decreases were associated with decreased metabolism in several regions of the frontal of these brain areas which are involved in the channeling of drive and affect.
Abstract: Decreased dopaminergic function has been postulated to underlie cocaine addiction. To examine the possibility that dysfunction of brain regions subserved by the dopamine system could promote cocaine self-administration, positron emission tomography and a dual-tracer approach was used to examine dopamine D2 receptor availability and regional brain glucose metabolism in cocaine abusers. When compared to normal controls, cocaine abusers showed significant decreases in dopamine D2 receptor availability which persisted 3-4 months after detoxification. Decreases in dopamine D2 receptor availability were associated with decreased metabolism in several regions of the frontal lobes, most markedly orbito-frontal cortex and cingulate gyri. Dopamine dysregulation of these brain areas which are involved in the channeling of drive and affect could lead to loss of control resulting in compulsive drug-taking behavior.
892 citations
TL;DR: The presence of reactive oxygen species in cells ensures that the oxidatively damaged base 8-oxoguanine will be generated at high frequency in the DNA of all living organisms.
780 citations
TL;DR: The stability of anandamide in serum and its rapid breakdown in cells and tissues are consistent with the observation that it is active when administered systemically, and its duration of action will be regulated by its rate of degradation in cells.
718 citations
592 citations
TL;DR: It appears that the NGF- induced mechanical hyperalgesia is brought about by different mechanisms in neonatal and adult rats.
Abstract: Recently, we have shown that the interaction between NGF and sensory neurons in early postnatal periods is restricted to nociceptive afferents (Ritter et al., 1991; Lewin et al., 1992a; Ritter and Mendell, 1992). Here we show that administration of excess NGF to neonatal or mature animals can lead to a profound behavioral hyperalgesia. Neonatal NGF treatment (postnatal day 0-14) resulted in a profound mechanical hyperalgesia that persisted until the animals had reached maturity (6 weeks of age). This hyperalgesia could be explained by an NGF-mediated sensitization of A delta nociceptive afferents to mechanical stimuli. This peripheral sensitization wore off with a time course similar to that of the behavior hyperalgesia. Treatment of animals from the second postnatal week until 5 weeks of age (juveniles) led to a very similar behavioral hyperalgesia; however, there was no corresponding sensitization of A delta nociceptors to mechanical stimuli. Finally, one group of adult animals (5 weeks old) was treated daily with single injections of NGF for between 1 and 4 d. Within 24 hr after the first NGF injection these animals developed a mechanical hyperalgesia of the same magnitude seen after neonatal and juvenile NGF treatments. No sensitization of A delta nociceptive afferents was observed in these animals. In addition to the mechanical hyperalgesia, the animals also developed a heat hyperalgesia after one injection of NGF. The heat hyperalgesia was apparent within 15 min after the injection; however, signs of mechanical hyperalgesia were not seen until 6 hr after the injection. In conclusion, it appears that the NGF-induced mechanical hyperalgesia is brought about by different mechanisms in neonatal and adult rats. Furthermore, in adult animals the NGF-induced mechanical and heat hyperalgesia also appear to be attributable to two different mechanisms. The mechanical hyperalgesia may be due to central changes (see Lewin et al., 1992b), whereas the heat hyperalgesia is likely to result at least in part from the sensitization of peripheral receptors to heat.
578 citations
TL;DR: In this article, the authors discuss the role of eDNA and in VITRO SYNTHESIS of INFECTIOUS VIRAL RNA in the selection and generation of mutants.
Abstract: INFECTIOUS eDNA AND IN VITRO SYNTHESIS OF INFECTIOUS VIRAL RNA 359 SELECTION AND GENERATION OF MUTANTS . . . . . . .... . . .. . . .. . . 360 Selection of Spontaneous Mutants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 Random Mutagenesis .... _ . . . . . . . _ _ .... ... ... _ _ . . . . . . . . . 370 Mutagenesis Targeted to Existing or de novo Introduced Restriction Sites . . . . 370 Oligonucleotide-mediated, Site Directed Mutagenesis. . . . . . . . . . . . . . . . . . 371 Exchange of Genomic Segments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371 In Search for Revertants . . . . .. . .. . . .. . . . . . . .. . . . . . .. ..... . . 372
TL;DR: Despite apparent changes in NGF's mode of action as the animal matures, it always interacts specifically with nociceptive sensory neurons and here it may serve as a link between inflammation and hyperalgesia.
TL;DR: This article found that voters' gender stereotypes have potentially negative implications for women candidates, especially when running for national office, despite the recent electoral success of female candiates in local, state, and national elections.
Abstract: Despite the recent electoral success of female candiates in local, state, and national elections, we find that voters' gender stereotypes have potentially negative implications for women candidates, especially when running for national office. We test the political impact of stereotypes by examining the relative importance of typical "male" and "female" personality traits and areas of issue competence for "good" politicians and a hypothetical candidate at different types and levels of office. Overall, we find a preference for "male" characteristics at higher levels of office. We attempt to reconcile the existence of gender stereotypes, which portray women candidates as insufficiently aggressive or less competent in their dealings with the military with the recent electoral success of women in national and statewide elections.
TL;DR: A 29-item fatigue assessment instrument is presented, its psychometric properties are described, and it is used to differentiate normal fatigue from fatigue related medical disorders.
TL;DR: The idea is that the dominant scattering is correctly described by a harmonic Hamiltonian, which is, in principle, transformable into a one-body problem of decoupled oscillators.
Abstract: As a crystal is disordered, a point may be reached where the typical mean free path of phonons is so short that the wavelength and mean free path are no longer sharp concepts, and the textbook phonon-gas model for thermal conductivity breaks down. This paper proposes an alternate theory for the disordered regime, and the subsequent paper implements the theory for a realistic model of amorphous silicon. The idea is that the dominant scattering is correctly described by a harmonic Hamiltonian, which is, in principle, transformable into a one-body problem of decoupled oscillators. From this the thermal conductivity can be exactly calculated by an analog of the Kubo-Greenwood formula for electrical conductivity of disordered metals. Anderson localization is correctly contained in this theory; localized states contribute no currents in harmonic approximation. What is required is an atomistic model with a large unit cell and periodic boundary conditions (to avoid undesired surface effects). The linear size of the model should be larger than the mean free paths of the dominant phonons. A Kubo formula and then a Kubo-Greenwood-type formula are derived for this problem. A ``mode diffusivity'' ${\mathit{D}}_{\mathit{i}}$ for the ith exact oscillator state is defined. The heat is carried by off-diagonal elements of the heat current operator, which have a nonzero contribution because the temperature gradient introduces nonzero off-diagonal elements of the density matrix 〈${\mathit{a}}_{\mathit{i}}^{\mathrm{\ifmmode^\circ\else\textdegree\fi{}}}$${\mathit{a}}_{\mathit{j}}$〉. An effort is made to interpret these results physically. Schemes for implementing this formalism are discussed.
TL;DR: In this paper, a random matrix model was constructed that, in the large-N limit, reduces to the low-energy limit of the QCD partition function put forward by Leutwyler and Smilga.
TL;DR: Comparison of inhibition titrations in combination with the analysis of the primary structures has enabled us to identify amino acid residues in cytochrome b that may be involved in the binding of the inhibitors and, by extrapolation, quinone/quinol.
TL;DR: This article is an expository description of quadratic rational maps from the Riemann sphere to itself and some examples of these maps are given.
Abstract: This article is an expository description of quadratic rational maps from the Riemann sphere to itself
TL;DR: Oral clindamycin and pyrimethamine are an effective treatment for toxoplasmic encephalitis and patients who have early neurologic deterioration despite treatment or who do not improve neurologically after 10 to 14 days of appropriate antitoxoplasma therapy should be considered candidates for brain biopsy.
Abstract: Background In patients with the acquired immunodeficiency syndrome (AIDS), toxoplasmic encephalitis is usually a presumptive diagnosis based on the clinical manifestations, a positive antitoxoplasma-antibody titer, and characteristic neuroradiologic abnormalities. A response to specific therapy helps to confirm the diagnosis, but it is unclear how rapid the response should be. We studied the course of patients treated for acute toxoplasmic encephalitis and evaluated objective clinical criteria for this empirical diagnosis. Methods A quantifiable neurologic assessment was used prospectively to evaluate the clinical outcome of patients with AIDS and toxoplasmic encephalitis who were treated with oral clindamycin (600 mg four times a day) and pyrimethamine (75 mg every day) for six weeks. Results Thirty-five of 49 patients (71 percent) responded to therapy, and 30 of these (86 percent) had improvement by day 7. Thirty-two of those with a response (91 percent) improved with respect to at least half of their base-line abnormalities by day 14. Improvement in neurologic abnormalities within 7 to 14 days after the start of therapy was strongly associated with the neurologic response at 6 weeks. The four patients in whom treatment failed and the two patients with lymphoma had progressing neurologic abnormalities or new abnormalities during the first 12 days of therapy. Nonlocalizing abnormalities (headache and seizure) improved regardless of the clinical outcome. Conclusions Oral clindamycin and pyrimethamine are an effective treatment for toxoplasmic encephalitis. Patients who have early neurologic deterioration despite treatment or who do not improve neurologically after 10 to 14 days of appropriate antitoxoplasma therapy should be considered candidates for brain biopsy.
TL;DR: In this article, the authors adopt a more fundamental view and extend the concept of stability to a variety of probabilistic schemes, which give rise to alternative stable distributions, which they compare empirically using S&P 500 stock return data.
Abstract: In the 1960's Benoit Mandelbrot and Eugene Fama argued strongly in favor of the stable Paretian distribution as a model for the unconditional distribution of asset returns. Although a substantial body of subsequent empirical studies supported this position, the stable Paretian model plays a minor role in current empirical work. While in the economics and finance literature stable distributions are virtually exclusively associated with stable Paretian distributions, in this paper we adopt a more fundamental view and extend the concept of stability to a variety of probabilistic schemes. These schemes give rise to alternative stable distributions, which we compare empirically using S&P 500 stock return data. In this comparison the Weibull distribution, associated with both the nonrandom-minimum and geometric-random summation schemes dominates the other stable distributions considered-including the stable Paretian model.
TL;DR: Although a majority of studies have found that male and female college teachers do not differ in the global ratings they receive from their students, when statistically significant differences are found, more of them favor women than men as mentioned in this paper.
Abstract: Although a majority of studies have found that male and female college teachers do not differ in the global ratings they receive from their students, when statistically significant differences are found, more of them favor women than men Across studies, the average association between gender and overall evaluation, while favoring women (averager=+02), is so small as to be insignificant in practical terms Considering specific instructional dimensions of evaluations, female teachers receive very slightly higher ratings on their sensitivity to and concern with class level and progress than do men (averager=+12) On other specific dimensions, men and women either do not differ or the differences are trivial in size (or, for two dimensions, while nontrivial, based on too few studies to be generalizable with any degree of certainty) Students tend to rate same-gendered teachers a little higher than opposite-gendered teachers Although interaction effects on evaluations have also been found between gender of teacher and other factors (academic rank of the teacher, academic area, class level of the course, difficulty of the teacher or course, and the teacher's pedagogical orientation or personality characteristics), they are inconsistent across studies Moreover, ratings of teachers are sometimes enhanced by gender-typical, and sometimes by gender-atypical, attributes, behaviors, and positions The findings are discussed in terms of the expectations or demands of students and whether or not student ratings are biased by the gender of the teacher
TL;DR: It is demonstrated that gelatinase/type IV collagenase activity is important in endothelial cell morphogenesis on Matrigel, and a role for collagenases in formation of new capillaries in vivo is suggested.
Abstract: It has been proposed that proteases are important in endothelial cell behavior. We examined the contribution of the gelatinase/type IV collagenase system in an in vitro model of endothelial differentiation. Human umbilical vein endothelial cells rapidly align and form networks of tubes when cultured on a basement membrane preparation, Matrigel. Zymograms of culture supernates demonstrate a 72-kD and a 92-kD gelatinase activity; the cells produce most of the 72-kD gelatinase, whereas the 92-kD activity is derived entirely from the Matrigel. Addition of antibodies against type IV gelatinase/collagenase decreases the area of the tube network. Both tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2, similarly decrease tube formation when added to cultures. Conversely, exogenous recombinant 72-kD gelatinase increases tube-forming activity. The effects of the anti-gelatinase antibodies and the TIMPs are not additive. Inhibition by either antibodies or TIMPs is greatest when they are added at culture initiation, suggesting that the protease activity is important in the early steps of morphogenesis. However, culture of the cells on Matrigel does not increase early expression of mRNA for the 72-kD gelatinase. Expression of message for the enzyme actually decreases during the course of the assay, while transcription of mRNAs for TIMPs increases, further supporting the concept that collagenases facilitate an early event in tube formation. These data demonstrate that gelatinase/type IV collagenase activity is important in endothelial cell morphogenesis on Matrigel, and suggest a role for collagenases in formation of new capillaries in vivo.
TL;DR: In this paper, the authors examined relationships between empowerment, supervisor's support for career development and components of career motivation: career resilience, career insight and career identity, and found that self-ratings of career identity may be composed of two independent dimensions, work identity and organization identity.
Abstract: This paper examines relationships between empowerment, supervisor's support for career development and components of career motivation: career resilience, career insight and career identity. In Study 1, self-ratings of career insight and identity from 183 employees were positively related to supervisor ratings of the degree to which the subordinate is empowered and receives support for career development. Self-ratings of empowerment and support for career development were related to supervisor ratings on all three career motivation variables. Study 2 collected supervisor and self-ratings of the same variables for another sample of 59 employees at two points in time with a 3½-month interval to examine the test–retest reliability of the measures and further study their interrelationships. The results supported the test–retest reliability of the measures, indicated that career identity may be composed of two independent dimensions, work identity and organization identity, and suggested that individuals who are higher on organizational identity are those who are rated lower on empowerment by their supervisors. The discussion considers directions for research on variables that affect perceptions of empowerment, support for career development and career motivation.
TL;DR: Repetitive activity in unmyelinated sensory afferent neurones, arising from electrical stimuli, tissue injury or nerve damage, can induce long-lasting sensitization in dorsal horn neurones and this process can be blocked by antagonists of the NMDA receptor.
TL;DR: During cutaneous wound repair, fibroblasts appear to progress through four phenotypes: first proliferating, second migrating, third synthesizing extracellular matrix molecules, and fourth expressing thick actin bundles as myofibroblast.
TL;DR: To analyze the development of glial progenitor cells in the developing rat cerebellum, immunofluorescent, immunocytochemical, and autoradiographic techniques were utilized.
Abstract: The development and differentiation of bipotential glial precursor cells has been studied extensively in tissue culture, but little is known about the distribution and fate of these cells within intact animals. To analyze the development of glial progenitor cells in the developing rat cerebellum, we utilized immunofluorescent, immunocytochemical, and autoradiographic techniques. Glial progenitor cells were identified with antibodies against the NG2 chondroitin-sulfate proteoglycan, a cell-surface antigen of 02A progenitor cells in vitro, and the distribution of this marker antigen was compared to that of marker antigens that identify immature astrocytes, mature astrocytes, oligodendrocyte precursors, and mature oligodendrocytes. Cells expressing the NG2 antigen appeared in the cerebellum during the last 3-4 days of embryonic life. Over the first 10 days of postnatal life, the NG2-labeled cells incorporated 3H-thymidine into their nuclei and their total number increased. At all ages examined, the NG2-labeled cells did not contain either vimentin-like or glial fibrillary acidic protein (GFAP)-like immunoreactivity, suggesting that they do not develop along an astrocytic pathway. NG2-labeled cells of embryonic animals expressed GD3 ganglioside antigens, a property of oligodendrocyte precursors, whereas NG2-positive cells of postnatal animals did not express GD3 immunoreactivity. Nevertheless, the NG2-labeled cells of the nascent white matter expressed oligodendrocyte-specific marker antigens. Cells lying outside of the white matter continued to express the NG2 antigen. In adult animals, the NG2-labeled cells incorporated 3H-thymidine. Glial cells isolated from adult animals and grown in tissue culture express the NG2 antigen and display the phenotypic plasticity characteristic of 02A progenitor cells. These findings demonstrate that a population of glial progenitor cells is extensive within both young and adult animals.
TL;DR: In this article, the complete O(αS) QCD corrections to the virtual-photon cross sections for heavy-flavour production in deep-elastic electron-proton scattering are presented.
TL;DR: It is demonstrated that phospholipase A2 and 5-lipoxygenase activities resulting in production of leukotrienes are required for bacterial entry and that S. typhimurium invasion stimulated a rapid increase in the levels of free intracellular calcium in cultured epithelial cells.