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Biomedical subjects

Y Goodman

Publications and source records attributed to Y Goodman.

18 recordsLinked to original sources
PubMed2001

Dynamics of inclusion and exclusion: comparing mental illness narratives of Haredi male patients and their rabbis.

By comparing versions of mental illness narratives - told by Haredi (Utraorthodox Jews) male patients of a mental health clinic in Israel and by their rabbis - this paper relates to two distinct, yet interrelated, theoretical questions: the place and agency of narrators, and the tension between experience and representation. A pair of narratives exemplifies a pattern in which the patients (Talmudic students) tell a narrative of a sudden breakdown related to a dramatic meeting with a non-human figure (often, a woman) or force. Their rabbis, by contrast, tell a narrative that emphasizes their students' mundane symptoms, "abnormal" and "immoral" behavior, and use a local adaptation of a Western psychological explanatory model. A dynamic of inclusion and exclusion emerges as students are seeking legitimization and avoidance of stigma, while their rabbis are silencing themes that challenge social and cultural orders. The different narratives are further interpreted in the context of the micropolitics of the interviews and of identity politics between the Haredim and secular Israelis. This social dynamics shows how differently placed social actors-narrators-interpreters construct differently contested and diverse cultural narratives of a seemingly shared reality.

Clergy↗
PubMed1998

Uric acid protects neurons against excitotoxic and metabolic insults in cell culture, and against focal ischemic brain injury in vivo.

Uric acid is a well-known natural antioxidant present in fluids and tissues throughout the body. Oxyradical production and cellular calcium overload are believed to contribute to the damage and death of neurons that occurs following cerebral ischemia in victims of stroke. We now report that uric acid protects cultured rat hippocampal neurons against cell death induced by insults relevant to the pathogenesis of cerebral ischemia, including exposure to the excitatory amino acid glutamate and the metabolic poison cyanide. Confocal laser scanning microscope analyses showed that uric acid suppresses the accumulation of reactive oxygen species (hydrogen peroxide and peroxynitrite), and lipid peroxidation, associated with each insult. Mitochondrial function was compromised by the excitotoxic and metabolic insults, and was preserved in neurons treated with uric acid. Delayed elevations of intracellular free calcium levels induced by glutamate and cyanide were significantly attenuated in neurons treated with uric acid. These data demonstrate a neuroprotective action of uric acid that involves suppression of oxyradical accumulation, stabilization of calcium homeostasis, and preservation of mitochondrial function. Administration of uric acid to adult rats either 24 hr prior to middle cerebral artery occlusion (62.5 mg uric acid/kg, intraperitoneally) or 1 hr following reperfusion (16 mg uric acid/kg, intravenously) resulted in a highly significant reduction in ischemic damage to cerebral cortex and striatum, and improved behavioral outcome. These findings support a central role for oxyradicals in excitotoxic and ischemic neuronal injury, and suggest a potential therapeutic use for uric acid in ischemic stroke and related neurodegenerative conditions.

Animals↗
PubMed1997

Activation of NF-kappaB protects hippocampal neurons against oxidative stress-induced apoptosis: evidence for induction of manganese superoxide dismutase and suppression of peroxynitrite production and protein tyrosine nitration.

The transcription factor NF-kappaB is expressed in neurons wherein it is activated in response to a variety of stress- and injury-related stimuli including exposure to cytokines such as tumor necrosis factor-alpha (TNFalpha), and excitotoxic and oxidative insults. NF-kappaB may play a role in the anti-death actions of TNFalpha in cultured hippocampal neurons exposed to metabolic and oxidative insults. We now report that pretreatment of hippocampal cell cultures with agents that activate NF-kappaB (TNFalpha and C2-ceramide) confers resistance of neurons to apoptosis induced by the oxidative insults FeSO4 and amyloid beta-peptide (Abeta25-35). The neuroprotective actions of TNFalpha and ceramide were abolished in cultures cotreated with kappaB decoy DNA demonstrating a requirement for NF-kappaB activation for prevention of cell death. Levels of manganese superoxide dismutase (Mn-SOD) in neurons were increased following exposure of cultures to TNFalpha and ceramide in control cultures, but not in cultures cotreated with kappaB decoy DNA. FeSO4 and Abeta25-35 induced accumulation of mitochondrial peroxynitrite, and membrane lipid peroxidation, in neurons. Peroxynitrite accumulation and lipid peroxidation were largely prevented in neurons pretreated with TNFalpha and ceramide prior to exposure to FeSO4 and Abeta25-35, an effect blocked by kappaB decoy DNA. Immunoreactivity of neurons with an anti-nitrotyrosine antibody was increased following exposure to FeSO4 and Abeta25-35; TNFalpha and C2-ceramide suppressed protein tyrosine nitration, and kappaB decoy DNA blocked the effects of TNFalpha and C2-ceramide. Finally, the peroxynitrite scavenger uric acid protected neurons against apoptosis induced by FeSO4 and Abeta, and suppressed peroxynitrite accumulation. We conclude that, by inducing production of Mn-SOD and suppressing peroxynitrite formation and membrane lipid peroxidation, NF-kappaB plays an anti-apoptotic role in neurodegenerative conditions that involve oxidative stress. The data further suggest important roles for peroxynitrite and NF-kappaB in the pathogenesis of neuronal degeneration in Alzheimer's disease.

Animals↗
PubMed1996

K+ channel openers protect hippocampal neurons against oxidative injury and amyloid beta-peptide toxicity.

Potassium channel openers (KCOs) such as diazoxide and levochromakalim can protect cardiac myocytes against ischemic injury and neurons against excitotoxic injury, presumably because of their ability to hyperpolarize the plasma membrane and reduce calcium influx. We now report that diazoxide, levocromakalim (LCC), and to a lesser extent pinacidil, protect cultured rat hippocampal neurons against oxidative injury induced by exposure to FeSO4 and amyloid beta-peptide (A beta). Imaging studies of intracellular peroxide levels revealed that KCOs suppressed the generation of peroxides induced by FeSO4 and A beta. KCOs were effective in protecting neurons against oxidative insults in the presence of the K+ channel blockers glibenclimide and 4-aminopyridine indicating that their protective mechanism involved actions in addition to activation of K+ channels. The data suggest that KCOs may be of therapeutic value in an array of neurodegenerative disorders that involve oxidative injury.

Amyloid beta-Peptides↗
PubMed1996

Bacterial alkaloids mitigate seizure-induced hippocampal damage and spatial memory deficits.

Studies of human patients with temporal lobe epilepsy and animal models of epilepsy have established relationships between seizures, excitotoxic hippocampal damage, and memory impairment. We report that bacterial alkaloids, recently shown to mimic actions of neurotrophic factors in cell culture, attenuate seizure-induced damage to hippocampal neurons and memory impairment in adult rats when administered subcutaneously. Intrahippocampal administration of convulsant doses of kainic acid (KA) to adult rats resulted in degeneration of neurons in CA3, CA1, and hilus. Rats administered KA exhibited (24 h later) deficits in performance on both goal latency and probe trial tasks in Morris water maze (MWM) tests of visuospatial memory. Seizure-induced damage to hippocampal neurons was significantly reduced, to varying extents, in rats administered the bacterial alkaloids K252a, K252b, or staurosporine (daily injections of 4 micrograms/kg body weight) prior to KA administration. The KA-induced deficits in MWM goal latency performance were abrogated in rats administered K252a or K252b, and K252a and staurosporine completely prevented seizure-induced impairment on the MWM probe trial. The alkaloids did not suppress electroencephalographic seizure activity, suggesting a dissociation between synchronization of activity and synaptically mediated excitotoxic injury to hippocampal neurons. Each alkaloid caused an increase in levels of protein tyrosine phosphorylation as determined by Western blot analysis of hippocampal tissue. Our data indicate that these bacterial alkaloids have potent antiexcitotoxic activities which may have clinical utility in epilepsy and other disorders that involve excitotoxic damage.

Alkaloids↗
PubMed1996

Ceramide protects hippocampal neurons against excitotoxic and oxidative insults, and amyloid beta-peptide toxicity.

The transcription factor NF kappa B is activated by various signals associated with brain injury, including tumor necrosis factor (TNF), oxidative insults, and amyloid beta-peptide (A beta). We recently reported that TNFs activate NF kappa B in neurons and protect them against excitotoxic and oxidative insults, including A beta toxicity. We now report that C2-ceramide (C2), a membrane-permeant activator of NF kappa B, protects cultured rat hippocampal neurons against death induced by glutamate, FeSO4, and A beta. Protection was concentration dependent, specific (a ceramide analogue known not to activate NF kappa B was ineffective), required pretreatment, and was blocked by inhibitors of RNA and protein synthesis. Lipid peroxidation and accumulation of cellular peroxides induced by glutamate, FeSO4, and A beta were significantly attenuated in neurons pretreated with C2. The data indicate that C2 induces antioxidant pathways in neurons and suggest novel approaches for reducing neuronal injury in both acute and chronic neurodegenerative conditions.

Amyloid beta-Peptides↗
PubMed1996

Estrogens attenuate and corticosterone exacerbates excitotoxicity, oxidative injury, and amyloid beta-peptide toxicity in hippocampal neurons.

Steroid hormones, particularly estrogens and glucocorticoids, may play roles in the pathogenesis of neurodegenerative disorders, but their mechanisms of action are not known. We report that estrogens protect cultured hippocampal neurons against glutamate toxicity, glucose deprivation, FeSO4 toxicity, and amyloid beta-peptide (A beta) toxicity. The toxicity of each insult was significantly attenuated in cultures pretreated for 2 h with 100 nM-10 microM 17 beta-estradiol, estriol, or progesterone. In contrast, corticosterone exacerbated neuronal injury induced by glutamate, FeSO4, and A beta. Several other steroids, including testosterone, aldosterone, and vitamin D, had no effect on neuronal vulnerability to the different insults. The protective actions of estrogens and progesterone were not blocked by actinomycin D or cycloheximide. Lipid peroxidation induced by FeSO4 and A beta was significantly attenuated in neurons and isolated membranes pretreated with estrogens and progesterone, suggesting that these steroids possess antioxidant activities. Estrogens and progesterone also attenuated A beta- and glutamate-induced elevation of intracellular free Ca2+ concentrations. We conclude that estrogens, progesterone, and corticosterone can directly affect neuronal vulnerability to excitotoxic, metabolic, and oxidative insults, suggesting roles for these steroids in several different neurodegenerative disorders.

Amyloid beta-Peptides↗
PubMed1995

Tumor necrosis factors alpha and beta protect neurons against amyloid beta-peptide toxicity: evidence for involvement of a kappa B-binding factor and attenuation of peroxide and Ca2+ accumulation.

In Alzheimer disease (AD) the amyloid beta-peptide (A beta) accumulates in plaques in the brain. A beta can be neurotoxic by a mechanism involving induction of reactive oxygen species (ROS) and elevation of intracellular free calcium levels ([Ca2+]i). In light of evidence for an inflammatory response in the brain in AD and reports of increased levels of tumor necrosis factor (TNF) in AD brain we tested the hypothesis that TNFs affect neuronal vulnerability to A beta. A beta-(25-35) and A beta-(1-40) induced neuronal degeneration in a concentration- and time-dependent manner. Pretreatment of cultures for 24 hr with TNF-beta or TNF-alpha resulted in significant attenuation of A beta-induced neuronal degeneration. Accumulation of peroxides induced in neurons by A beta was significantly attenuated in TNF-pretreated cultures, and TNFs protected neurons against iron toxicity, suggesting that TNFs induce antioxidant pathways. The [Ca2+]i response to glutamate (quantified by fura-2 imaging) was markedly potentiated in neurons exposed to A beta, and this action of A beta was suppressed in cultures pretreated with TNFs. Electrophoretic mobility-shift assays demonstrated an induction of a kappa beta-binding activity in hippocampal cells exposed to TNFs. Exposure of cultures to I kappa B (MAD3) antisense oligonucleotides, a manipulation designed to induce NF-kappa B, mimicked the protection by TNFs. These data suggest that TNFs protect hippocampal neurons against A beta toxicity by suppressing accumulation of ROS and Ca2+ and that kappa B-dependent transcription is sufficient to mediate these effects. A modulatory role for TNF in the neurodegenerative process in AD is proposed.

Amyloid beta-Peptides↗
PubMed1995

Different amyloidogenic peptides share a similar mechanism of neurotoxicity involving reactive oxygen species and calcium.

The amyloid beta-peptide (A beta) that accumulates as insoluble plaques in the brains of Alzheimer's victims can be neurotoxic, by a mechanism that may involve generation of reactive oxygen species (ROS) and destabilization of cellular calcium homeostasis. We now provide evidence that the mechanism of neurotoxicity of two other amyloidogenic peptides (APs), human amylin and beta 2-microglobulin, also involves induction of ROS and elevation of [Ca2+]i. Human amylin, beta 2-microglobulin and A beta 1-40 all caused significant death of neurons in rat hippocampal cell cultures during 24-48 h exposure periods. Rat amylin, a non-AP, was not neurotoxic. Each AP caused an elevation of rest [Ca2+]i during a 20 h exposure period, and promoted a sustained elevation of [Ca2+]i following exposure to glutamate which was significantly greater than controls. Each AP induced accumulation of ROS in neurons which preceded elevation of [Ca2+]i. Several antioxidants, including propyl gallate, vitamin E and the spin-trapping compound N-tert-butyl-alpha-phenylnitrone attenuated the elevation of [Ca2+]i and neurotoxicity induced by the peptides. The data indicate that different APs share a common mechanism of neurotoxicity involving free radical accumulation and destabilization of [Ca2+]i homeostasis.

Amyloid↗
PubMed1995

Basic fibroblast growth factor selectively increases AMPA-receptor subunit GluR1 protein level and differentially modulates Ca2+ responses to AMPA and NMDA in hippocampal neurons.

The excitatory neurotransmitter glutamate is believed to play important roles in development, synaptic plasticity, and neurodegenerative conditions. Recent studies have shown that neurotrophic factors can modulate neuronal excitability and survival and neurite outgrowth responses to glutamate, but the mechanisms are unknown. The present study tested the hypothesis that neurotrophic factors modulate responses to glutamate by affecting the expression of specific glutamate-receptor proteins. Exposure of cultured embryonic rat hippocampal cells to basic fibroblast growth factor (bFGF) resulted in a concentration-dependent increase in levels of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-receptor subunit GluR1 protein as determined by western blot, dot-blot, and immunocytochemical analyses. In contrast, bFGF did not alter levels of GluP2/3, GluR4, or the NMDA-receptor subunit NR1. Nerve growth factor did not affect GluR1 levels. Calcium-imaging studies revealed that elevation of [Ca2+]i, resulting from selective AMPA-receptor activation, was enhanced in bFGF-pretreated neurons. On the other hand, [Ca2+]i responses to NMDA-receptor activation were suppressed in bFGF-treated neurons, consistent with previous studies showing that bFGF can protect neurons against NMDA toxicity. Moreover, neurons pretreated with bFGF were relatively resistant to the toxicities of glutamate and AMPA, both of which were shown to be mediated by NMDA receptors. These data suggest that differential regulation of the expression of specific glutamate-receptor subunits may be an important mechanism whereby neurotrophic factors modulate activity-dependent neuronal plasticity and vulnerability to excitotoxicity.

Animals↗
PubMed1994

Nordihydroguaiaretic acid protects hippocampal neurons against amyloid beta-peptide toxicity, and attenuates free radical and calcium accumulation.

Recent findings indicate that amyloid beta-peptide (A beta) can be neurotoxic by a mechanism involving an increase in the concentration of intracellular free Ca2+ ([Ca2+]i) and the generation of free radicals. In the present study, the lipoxygenase inhibitor/antioxidant nordihydroguaiaretic acid (NDGA) protected cultured rat hippocampal neurons against the toxicity of A beta in a concentration-dependent manner. Measurements of cellular oxidation (using the oxidation-sensitive dye 2,7-dichlorofluorescin) and intracellular free Ca2+ levels (using the Ca2+ indicator dye fura-2), showed that NDGA suppressed A beta-induced accumulation of reactive oxygen species (ROS) and Ca2+; Ca2+ responses to glutamate were also suppressed by NDGA. NDGA prevented neuronal injury and accumulation of ROS induced by iron, indicating a role for NDGA as an antioxidant in NDGA-mediated neuroprotection. Another lipoxygenase inhibitor (AA861) also protected against A beta and iron toxicity whereas the the 5-lipoxygenase-activating protein inhibitor L655,238 and the cyclooxygenase inhibitor indomethacin were ineffective. These findings suggest that NDGA can interupt a neurodegenerative pathway relevant to the pathophysiology of Alzheimer's disease.

Amyloid beta-Peptides↗
PubMed1994

Neurotrophin-4/5 protects hippocampal and cortical neurons against energy deprivation- and excitatory amino acid-induced injury.

Neurotrophin-4/5 (NT-4/5) is a recently discovered member of the neurotrophin family of neurotrophic factors which includes NGF, BDNF and NT-3. NT-4/5 is expressed in the brain where its function is unknown. We have found that NT-4/5 can protect cultured embryonic rat hippocampal and cortical neurons against glucose deprivation-induced injury. Significant protection was observed with NT-4/5 concentrations from 100-1000 ng/ml, with a dose-response curve similar to that of BDNF. Neuronal vulnerability to glutamate toxicity was significantly reduced in cultures pretreated with NT-4/5. Moreover, neurons pretreated with NT-4/5 were more resistant to toxicity induced by calcium ionophore A23187, demonstrating that NT-4/5 increases neuronal resistance to calcium-mediated injury. These data indicate that, as with other neurotrophins, NT-4/5 may serve a neuroprotective function in the brain.

Animals↗
PubMed1994

Staurosporine and K-252 compounds protect hippocampal neurons against amyloid beta-peptide toxicity and oxidative injury.

Recent studies have shown that amyloid beta-peptide (A beta) can be directly neurotoxic by a mechanism related to secondary structure of the peptide, and mediated by free radical production and an increase in the concentration of intracellular free calcium ([Ca2+]i). We now report that staurosporine and K-252 compounds, low molecular weight alkaloids of bacterial origin, can protect cultured rat hippocampal neurons against the toxicity of A beta in a concentration-dependent manner. The alkaloids also protected neurons against iron-induced (free radical-mediated) injury. Measurements of [Ca2+]i using fura-2 imaging revealed that the elevation of [Ca2+]i that occurred in response to long-term exposure to A beta was attenuated in neurons treated with staurosporine and K-252 compounds. These findings indicate that staurosporine and K-252 compounds can interupt a neurodegenerative pathway relevant to the pathophysiology of Alzheimer's disease.

Alkaloids↗
PubMed1994

Secreted forms of beta-amyloid precursor protein protect hippocampal neurons against amyloid beta-peptide-induced oxidative injury.

Alternative processing of the beta-amyloid precursor protein (beta APP) can result in liberation of either secreted forms of beta APP (APPSs), which may play roles in neuronal plasticity and survival, or amyloid beta-peptide (A beta), which can be neurotoxic. In rat hippocampal cell cultures A beta 1-40 caused a time- and concentration-dependent reduction in neuronal survival. APPS695 and APPS751 significantly reduced A beta-induced injury in a concentration-dependent manner. A beta caused an elevation of intracellular calcium levels ([Ca2+]i) which was significantly attenuated by APPSs. A beta also caused induction of reactive oxygen species (measured using the oxidation-sensitive fluorescent dye 2,7-dichlorofluorescein) which was also attenuated by APPSs. A beta-induced neurotoxicity and elevations of [Ca2+]i were attenuated by vitamin E, suggesting the involvement of free radicals in A beta-induced loss of calcium homeostasis and neuronal injury. The APPSs protected neurons against oxidative injury caused by exposure to iron. Taken together, the data indicate that A beta kills neurons by causing free radical production and increased [Ca2+]i. APPSs can protect neurons against such free radical- and Ca(2+)-mediated injury. These findings support the hypothesis that altered processing of beta APP contributes to neuronal injury in Alzheimer's disease.

Amyloid beta-Peptides↗
PubMed1993

The development and implementation of a respite care program for paediatric peritoneal dialysis patients.

When a child is sent home on peritoneal dialysis, the family is faced with enormous challenges. Despite the coordination of community resources, there are few opportunities for relief from the many tasks required to keep a child home on dialysis. The intensity and duration of the home care required for children awaiting renal transplantation have often led to overwhelming parental stress, marital discord and burn-out. These events can lead to the detriment of the well-being of the child and may result in a higher incidence of peritonitis. Many families had identified the need for some form of relief. Recognizing this, the staff of the home dialysis program of the Toronto Hospital for Sick Children (HSC) joined forces with the staff at Bloorview Children's Hospital (a chronic care/rehabilitation centre) to develop a respite program for these families. The HSC staff provided staff education, medical back-up and financed the equipment and supply costs while the Bloorview Hospital provided the accommodation and the medical and nursing staff to care for the children. In addition to providing parental relief, Bloorview Hospital was able to provide extended care to children requiring peritoneal dialysis until their parents were able to care for them at home. This enabled HSC to use their beds for more acutely ill children. Initial evaluation of the program was favourable and efforts are now being made to streamline the system.

Child↗
PubMed1992

The peritoneal equilibration test in children.

The peritoneal equilibration test (PET) has been recommended in adults as a standardized means of estimating solute transport. Based on results of the PET, adult peritoneal permeability has been classified as high, high average, low average, and low. We performed a PET on 32 children aged 0.8 to 17.8 years (mean 9.3) using a dwell volume of 32 +/- 5 ml/kg of 2.5% dialysate. Dialysate to plasma (D/P) ratios for creatinine, urea, and sodium were calculated at two and four hours as were the ratios of dialysate glucose at two and four hours to the dialysate glucose at time 0 (D/Do). Stepwise logistic regression identified only the patients' age and D/Do glucose values at two hours as significant predictors of ultrafiltration. Net ultrafiltration after a four hour dwell could be predicted for 75% of children above 9.3 years, or whose D/Do glucose value at two hours was greater than 0.45. The mean and standard deviation values for D/Do glucose and D/P creatinine at four hours were 0.31 +/- 0.17 and 0.71 +/- 0.12, respectively. When children are characterized according to adult standards, at least 70% fall into the high or high average permeability categories.

Adolescent↗
PubMedDate not supplied

Anticonvulsants attenuate amyloid beta-peptide neurotoxicity, Ca2+ deregulation, and cytoskeletal pathology.

Increasing evidence supports the involvement of amyloid beta-peptide (A beta) and an excitotoxic mechanism of neuronal injury in the pathogenesis of Alzheimer's disease. However, approaches aimed at preventing A beta toxicity and neurofibrillary degeneration are undeveloped. We now report that anticonvulsants (carbamazepine, phenytoin, and valproic acid) can protect cultured rat hippocampal neurons against A beta- and glutamate-induced injury. Each of the anticonvulsants attenuated the elevation of intracellular free calcium levels [(Ca2+)i] elicited by A beta or glutamate suggesting that their neuroprotective mechanism of action involved stabilization of [Ca2+]i. These compounds were effective at clinically relevant concentrations (carbamazepine, 100 nM-10 microM; phenytoin, 100 nM-1 microM; valproic acid, 100 nM-100 microM). The anticonvulsants suppressed glutamate-induced alterations in tau and buiquitin immunoreactivities. Compounds that stabilize [Ca2+]i may afford protection against the kinds of insults believed to underlie neuronal injury in Alzheimer's disease.

Amyloid beta-Peptides↗