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J H Weiss

Publications and source records attributed to J H Weiss.

At least 55 records · Page 3Linked to original sources
PubMed1990

The calcium channel blocker nifedipine attenuates slow excitatory amino acid neurotoxicity.

High concentrations of potent N-methyl-D-aspartate (NMDA) agonists can trigger degeneration of cultured mouse cortical neurons after an exposure of only a few minutes; in contrast, selective non-NMDA agonists or low levels of NMDA agonists require exposures of several hours to induce comparable damage. The dihydropyridine calcium channel antagonist nifedipine was used to test whether this slow neurotoxicity is mediated by a calcium influx through voltage-gated channels. Nifedipine had little effect on the widespread neuronal degeneration induced by brief exposure to high concentrations of NMDA but substantially attenuated the neurotoxicity produced by 24-hour exposure to submaximal concentrations of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate, kainate, or quinolinate. Calcium ion influx through dihydropyridine-sensitive, voltage-dependent calcium channels may be an important step in the neuronal injury induced by the prolonged activation of NMDA or non-NMDA glutamate receptors.

Animals↗
PubMed1990

Cortical neurons containing somatostatin- or parvalbumin-like immunoreactivity are atypically vulnerable to excitotoxic injury in vitro.

We exposed murine cortical neuronal cell cultures for 24 hours to defined concentrations of N-methyl-D-aspartate (NMDA), kainate, or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and assessed the resultant neuronal degeneration quantitatively by the efflux of lactate dehydrogenase to the bathing medium. The small subpopulations of neurons that stained immunohistochemically for either somatostatin- or parvalbumin-like reactivity were atypically affected by these excitotoxins. Limited exposure to kainate or AMPA did little damage to the general neuronal population, but destroyed nearly all somatostatin- or parvalbumin-reactive cells. Conversely, these immunoreactive cells were more resistant to NMDA-induced injury than the general population. In view of reports suggesting that somatostatin- and parvalbumin-reactive cortical neurons may be preferentially damaged in Alzheimer's disease, these observations support a hypothesis that the overactivation of non-NMDA receptors could be involved in Alzheimer's disease pathogenesis.

Animals↗
PubMed1989

Neurotoxicity of beta-N-methylamino-L-alanine (BMAA) and beta-N-oxalylamino-L-alanine (BOAA) on cultured cortical neurons.

Recent studies have implicated the ingestion of the structurally related plant excitotoxins, beta-N-methylamino-L-alanine (BMAA), and beta-N-oxalylamino-L-alanine (BOAA), in the pathogenesis of two human motor system diseases, the amyotrophic lateral sclerosis-Parkinsonism-dementia complex of Guam (Guam ALS-PD), and lathyrism, respectively. We have investigated the toxicity of these amino acids on cultured mouse cortical neurons in the presence of physiological concentrations of bicarbonate (a required toxic cofactor for BMAA neurotoxicity). A 24 h exposure to 10 microM - 3 mM BMAA, or to 300 nM - 100 microM BOAA, induced, concentration-dependent neuronal degeneration without glial damage; the neurotoxic EC50 for BMAA was about 1 mM, and the EC50 for BOAA was about 20 microM. At high concentrations, both compounds destroyed essentially the entire neuronal population. Neurotoxicity also depended on exposure duration, with reduced injury at an exposure time of 1 h, and increased injury at an exposure time of 3 days. Despite the fact that ingestion of BMAA and BOAA both lead to motor system damage, previous studies have suggested that the two excitotoxins act primarily on different glutamate receptor subtypes: BMAA on N-methyl-D-aspartate (NMDA) receptors, and BOAA on non-NMDA receptors. Consistent with these studies, the neurotoxicity of high concentrations of BMAA was substantially attenuated by 1 mM D-amino-5-phosphonovalerate (D-APV), whereas BOAA neurotoxicity was less sensitive to D-APV but was attenuated by 2 mM kynurenate.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids, Diamino↗
PubMed1989

Zinc and LTP.

Explore the source record for details and available documents.

Action Potentials↗
PubMed1989

Bicarbonate dependence of glutamate receptor activation by beta-N-methylamino-L-alanine: channel recording and study with related compounds.

beta-N-methylamino-L-alanine (BMAA) is a neurotoxic glutamate agonist possibly responsible for the neuronal degeneration found in the Guam amyotrophic lateral sclerosis-Parkinsonism-dementia complex. The basis for glutamate receptor activation by BMAA has been unclear, as BMAA lacks the omega electronegative moiety characteristic of other excitatory amino acids. We recently reported that the neuroexcitatory and neurotoxic effects of BMAA depend strongly on the presence of bicarbonate ions and proposed that an interaction between bicarbonate and the beta amino group of BMAA produces a molecular configuration appropriate for activating glutamate receptors. We now report that bicarbonate potentiates the ability of BMAA to open NMDA receptor-activated channels in isolated membrane patches. Furthermore, the neurotoxic and neuroexcitatory effects of two structural analogs of BMAA, DL-2,4-diaminobutyrate and DL-2,3-diaminopropionate, were also potentiated by bicarbonate. These findings support the bicarbonate cofactor hypothesis for BMAA action and provide direct evidence that it may be generalizable to certain other compounds.

Amino Acids, Diamino↗
PubMed1988

Beta-N-methylamino-L-alanine neurotoxicity: requirement for bicarbonate as a cofactor.

Ingestion of the excitotoxic cycad seed amino acid beta-N-methylamino-L-alanine may be responsible for the neuronal degeneration associated with Guam amyotrophic lateral sclerosis-parkinsonism-dementia in man. However, the basis for the central neurotoxicity of beta-N-methylamino-L-alanine has been unclear, as it lacks the omega acidic (or equivalent electronegative) moiety characteristic of other excitatory amino acids. beta-N-methylamino-L-alanine produced neurotoxic and neuroexcitatory effects in murine cortical cell cultures only when physiological concentrations of bicarbonate were available in the extracellular bathing medium. Bicarbonate may interact noncovalently with beta-N-methylamino-L-alanine to produce, in combination, a molecular configuration that activates glutamate receptors.

Amino Acids, Diamino↗
PubMed1988

Adenosine reduces cortical neuronal injury induced by oxygen or glucose deprivation in vitro.

The endogenous neuromodulatory purine, adenosine, substantially attenuated neuronal degeneration when added to dissociated cortical cell cultures acutely deprived of either oxygen or glucose. The protective effect of adenosine, was concentration-dependent between 30 and 1000 microM (EC50 about 100 microM), and could be mimicked by the stable adenosine analogue N6-cyclohexyladenosine (10 microM). Unlike postsynaptic glutamate receptor antagonists, which also block these forms of neuronal injury, adenosine did not alter the neurotoxicity of exogenously applied glutamate.

Adenosine↗
PubMed1987

N-methyl-D-aspartate receptors mediate hypoxic neuronal injury in cortical culture.

The ability of several glutamate receptor antagonists to reduce hypoxic cortical neuronal injury was quantitatively examined in cell cultures derived from fetal mice. Cultures exposed to hypoxia for 8 hr showed by the following day widespread neuronal injury, which was substantially attenuated by addition of the specific N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (APV). The protective effect of APV was concentration dependent (ED50 about 2 microM) and stereospecific (D-APV approximately 100 times more potent that L-APV). Neuron-protective effects were also observed with several other NMDA antagonists: 2-amino-7-phosphonoheptanoate, phencyclidine and (+)-SKF 10,047 [(+)-N-allylnormetazocine]--as well as with the nonspecific glutamate antagonists D-glutamylglycine and kynurenate. In addition, a similar antagonist profile was observed with a chemical model of hypoxic neuronal injury, produced by brief exposure to high concentrations of cyanide. In contrast, 1 mM concentrations of glutamate diethylester and gamma-aminomethyl sulfonate, compounds reported in some studies to preferentially antagonize non-NMDA glutamate receptors, failed to protect neurons against either hypoxia or cyanide. These results are consistent with the hypothesis that NMDA receptors are preferentially involved in the pathogenesis of hypoxic cortical neuronal injury and suggest that cortical cell culture may be a useful system in which to quantitatively characterize the pharmacology of that injury.

2-Amino-5-phosphonovalerate↗
PubMed1980

Focal and segmental glomerular sclerosis in reflux nephropathy.

Reflux nephropathy was diagnosed in 23 patients (14 per cent of all the patients who received transplants) between 1973 and 1977, and nephrectomy was performed in all. Histology and immunofluorescence revealed a glomerular sclerosis associated with the idiopathic nephrotic syndrome. No focal and segmental glomerular sclerosis was seen in kidneys removed from patients with nonglomerular renal disease. Twenty-four hour urinary protein excretion in grams was 3.1 +/- 0.3 (mean +/- SEM) and was greater than that in our patients with end-stage nonglomerular renal disease. Thirty-one renal transplants were performed in these 23 patients; thereafter, maximum protein excretion was 1.4 g. Focal and segmental glomerular sclerosis was seen in only one (chronic rejection, protein excretion less than 0.5) of the 20 kidneys available for histologic study. Thus, focal and segmental glomerular sclerosis is extremely common in reflux nephropathy, accounts for "glomerular" proteinuria and may contribute importantly to progressive renal failure but, unlike that associated with the idiopathic nephrotic syndrome, rarely recurs after renal transplantation.

Adolescent↗
PubMed1978

A possible relationship between Henoch-Schonlein syndrome and IgA nephropathy (Berger's disease). An illustrative case.

A 29-year-old white male with the Henoch-Schonlein syndrome and rapidly progressive glomerulonephritis received a kidney transplant. Postransplant, a glomerulonephritis histologically and immunologically indistinguishable from IgA nephropathy (Berger's disease) developed in the absence of any extrarenal manifestations of the Henoch-Schonlein syndrome. A possible pathogenetic interrelationship between these two diseases is discussed.

Adult↗