PubMed Health⌕ Search

Biomedical subjects

P E Schulz

Publications and source records attributed to P E Schulz.

18 recordsLinked to original sources
PubMed2005

Prevalence and patterns of cognitive impairment in sporadic ALS.

OBJECTIVE: To investigate the prevalence and nature of cognitive changes associated with sporadic amyotrophic lateral sclerosis (ALS) using a large scale study. METHODS: Consecutive patients with sporadic ALS (n = 279) underwent comprehensive neurologic evaluation and neuropsychological testing. Testing data from normal controls (n = 129) were used for classification and comparison purposes. RESULTS: On non-motor, non-speed-dependent tasks, 51% of patients with ALS had evidence of cognitive impairment compared to 5% of controls. Cluster analysis suggested four patient subgroups: 49% intact, 32% with mild impairment, 13% with moderate impairment, and 6% with severe impairment. Forty-one patients (15%) met criteria for frontotemporal dementia (FTD). ALS patient subgroups, excluding the intact group, performed significantly lower on tests of executive function and memory than normal controls. Patients with more severe disease also had deficits in confrontation naming. Although memory function declined with increasing severity of overall cognitive impairment, only two patients had the severe memory loss typical of Alzheimer disease. Cognitive impairment was correlated with clinical measures of word-finding, phrase length, and motor programming. Cognitive impairment was not correlated with depression scores or severity or duration of motor or bulbar symptoms. Patients with bulbar vs limb-onset ALS were not different in either level of impairment or pattern of performance. CONCLUSIONS: These data confirm the presence of cognitive impairment in 50% of patients with ALS and particularly implicate executive dysfunction and mild memory decline in the disease process. More severe impairment occurs in a subset of patients with ALS and has features consistent with FTD.

Adult↗
PubMed1997

Long-term potentiation involves increases in the probability of neurotransmitter release.

There is great interest in understanding the mechanisms of expression underlying long-term potentiation (LTP). They are agreed to involve an increase in synaptic efficacy, which is described by three multiplicative parameters: p, the probability of neurotransmitter release; n, the number of active release sites; and q, the postsynaptic unit response to transmitter release. We report three new lines of evidence suggesting that increases in p contribute to LTP expression. (i) When the contributions to LTP by p, n, and q are maximized, and p alone is decreased, another high-frequency stimulation elicits additional LTP. The additional potentiation is only associated with decreases in paired-pulse facilitation (PPF) suggesting an increase in p. (ii) There is an inverse relationship between baseline p [corrected] and the magnitude of LTP elicited, consistent with p [corrected] having more or less room to increase when p is smaller or greater. (iii) It has been shown that there is an inverse relationship between the magnitude of LTP induced and the associated changes in PPF. Now I find that decreasing p before inducing LTP moves the set-point for measuring those changes in PPF from before to after p is decreased, which would only occur if p contributes to LTP. Three lines of evidence, then, suggest that increases in p contribute to LTP expression, which is consistent with a presynaptic contribution to LTP. These experiments do not address potential postsynaptic contributions.

2-Amino-5-phosphonovalerate↗
PubMed1997

Neuroendocrine correlates of emotional reactivity and coping in male rats from the Roman high (RHA/Verh)- and low (RLA/Verh)-avoidance lines.

The Roman high (RHA/Verh)- and low (RLA/Verh)-avoidance rats, originally selected and bred for rapid vs. poor acquisition of a two-way active avoidance response, differ in emotional reactivity and sensitivity to stressors in various other test situations. These behavioral differences are associated with particular neuroendocrine and neurochemical characteristics. The aim of this short review is to present data currently available on the neuroendocrine profiles of RHA/Verh and RLA/Verh rats, together with more recent findings which suggest that differences in peripheral and central hormonal responses, and in hormone action on the brain, may be closely related to emotional reactivity and coping ability. Although genetic factors certainly play a major role, there is also evidence that epigenetic factors, e.g., early environmental influences, can modulate the phenotypic expression of the basic behavioral and neuroendocrine traits characterizing these lines. These psychogenetically selected lines can therefore be used as a model to investigate interactions between genes and the environment in determining each individual's sensitivity to stress and coping abilities ("vulnerability" model). This model may prove particularly useful for studies on the etiology and pathophysiology of anxiety and affective disorders and their neuroendocrine correlates.

Adaptation, Psychological↗
PubMed1997

Brain metabolism of progesterone, coping behaviour and emotional reactivity in male rats from two psychogenetically selected lines.

Brain metabolites of progesterone such as tetrahydroprogesterone (THP) act on GABAA receptors and have anxiolytic properties. The formation of THP and its 5 alpha-reduced precursor, dihydroprogesterone (DHP) was measured in vitro in various microdissected brain areas obtained from males of two psychogenetically selected rat lines, i.e. the Roman High-(RHA/Verh) and low-(RLA/Verh) Avoidance rats, which are known to differ in emotional reactivity and/or anxiety. The behavioural and neuroendocrine responses of these rats were also measured following exposure to a novel environment in two different test situations. The formation of DHP and THP was found to be significantly higher in the frontal cortex (FCX), and DHP in the bed nucleus of the stria terminalis (BST), of the hypoemotional RHA/Verh rats. In addition, enzymatic activity in the FCX was found to be inversely correlated with behavioural measures of anxiety. These results suggest that individual, possibly genetically-determined differences in brain production of endogenous anxiolytics derived from progesterone may account at least in part for the behavioural differences characterizing these two lines, and provide further evidence that neurosteroids acting on the GABAergic system may play an important role in modulating physiological and/or behavioural responses to environmental stressors.

20-alpha-Dihydroprogesterone↗
PubMed1997

Differing mechanisms of expression for short- and long-term potentiation.

Long-term potentiation (LTP) is a use-dependent form of synaptic plasticity that is of great interest as a cellular mechanism that may contribute to memory storage. It is the sustained phase of population excitatory postsynaptic potential induced by high-frequency stimulation (HFS). HFS can also induce short-term potentiation (STP), a decremental potentiation lasting approximately 15 min. It has been unclear whether STP is simply a reversible form of LTP elicited by subthreshold stimuli or whether it is an independently expressed form of synaptic plasticity. We have attempted to clarify the relationship between LTP and STP in the extracellular recording technique in area CA1 of the adult rat hippocampal slice preparation to test four predictions of the hypothesis that LTP and STP are expressed via the same mechanism. First, occluding LTP expression should block STP expression. Saturating LTP under six different conditions, however, did not occlude STP expression. Second, occluding STP expression should occlude LTP expression. The partial or full occlusion of STP by two maneuvers (increasing the stimulus intensity used for HFS or applying 3-isobutyl-1-methylxanthine), however, did not occlude LTP expression. Third, LTP increases and decreases paired-pulse facilitation (PPF), and STP should have the same effect. STP did not change PFF, however. The first three results, then, suggest that STP and LTP are expressed via different mechanisms. Fourth, STP should be maximal near the LTP induction threshold, and then decrease above it. Surprisingly, STP was maximal at or very close to the LTP induction threshold, but it did not decrease above this threshold. This relationship suggests the possibility that STP and LTP share an induction step(s). What is the function of the independently expressed STP? We find that LTP can be induced by two HFSs, each of which is subthreshold for LTP, if the second is given during STP from the first. This suggests that STP can temporarily lower the LTP induction threshold. Three lines of evidence, then, suggest that STP and LTP may be expressed via different mechanisms; however, the proximity of STP saturation to LTP induction suggests that they may share an induction step(s). STP may also have the very important function of temporarily lowering the LTP induction threshold. Finally, these data suggestion caution in interpreting LTP data obtained <20-30 min after HFS, because they may be contaminated by STP, which appears to have different underlying mechanisms.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Using paired-pulse facilitation to probe the mechanisms for long-term potentiation (LTP).

Paired-pulse facilitation (PPF) of excitatory synaptic transmission at Schaffer collateral synapses in the hippocampus was examined in relationship to long-term potentiation (LTP). PPF is a relatively simple-to-measure presynaptic form of synaptic plasticity. It is hypothesized that if the expression of LTP includes a presynaptic component, then PPF and LTP may interfere with one another. When averaged over more than 100 experiments, we observed no change in average PPF with LTP, as reported previously by a number of investigators. When individual experiments were analyzed, however, PPF significantly increased or decreased with LTP in direct relation to the initial value of PPF. There was also a linear relationship between the change in PPF and the magnitude of LTP. The PPF changes were specific to LTP and presynaptic in origin as they were input-specific and persisted with low concentrations of CNQX, GABAA and GABAB antagonists, different interstimulus intervals, and different Ca2+ concentrations. To understand the interaction between LTP and PPF, we constructed a simple model of LTP in which potential contributions by increases in three synaptic parameters were examined: the number of neurotransmitter release sites (n), the probability of release (p), and the postsynaptic unit potential (q). The data were fit by a model in which there were increases in n that changed the average p of the population, but not by a model that increased p or q alone. This is the first experimental evidence for an increase in the number of release sites with LTP, which could be due to pre- or postsynaptic mechanisms.

Animals↗
PubMed1995

Differential nitric oxide synthase activity in human platelets during normal pregnancy and pre-eclampsia.

1. Nitric oxide released from endothelial cells is a potent vasodilator that might play an important role in cardiovascular regulation during pregnancy. Platelets, like endothelial cells, contain a constitutive form of nitric oxide synthase. 2. The present study aimed to measure the activity of this nitric oxide-forming enzyme in normotensive pregnant and non-pregnant women, as well as in women who had developed pre-eclampsia. Nitric oxide synthase activity was measured in the platelets of 21 normotensive pregnant women, 16 non-pregnant women and seven pregnant women who had developed pre-eclampsia. 3. The nitric oxide synthase activity was significantly higher in normotensive pregnant women [36.8 +/- 2.7 pmol h-1 mg-1 of protein (mean +/- SEM), P < 0.001] than in non-pregnant control subjects (16.8 +/- 1.4 pmol h-1 mg-1 of protein) and in women with pre-eclampsia (24.5 +/- 2.1 pmol h-1 mg-1 of protein, P < 0.01). 4. These data suggest that nitric oxide synthesis is increased during normal pregnancy, possibly contributing to the vasodilatation associated with this condition. Nitric oxide generation, however, may be inappropriately low in pregnant women developing pre-eclampsia, thus leading to an enhanced vasoconstriction.

Adult↗
PubMed1995

Adrenergic control of rat pineal NO synthase.

We have previously shown that exposure of rats to constant light (LL) induced a decrease in NO synthase (NOS) activity in the pineal gland. We present here the evidence that chronic (5 days) norepinephrine (NE) or isoproterenol treatment prevents the effect of LL and enhances pineal NOS activity in LL animals. This effect of NE appears to be mediated by beta-adrenoceptors, because it was not mimicked by the alpha-agonist phenylephrine. Pineal NOS activity was reduced in 16-h light/8-h dark animals treated for 4 days with the beta-adrenergic antagonist propranolol but not with the alpha 1-antagonist prazosin, indicating again an involvement of beta-adrenergic receptor in the control of NOS. Treatment with adrenergic antagonists did not affect cortical NOS activity, suggesting that the control of NOS is different in these two tissues or that the pineal expresses a specific isoform of the enzyme. Taken together, these data suggest that NE controls NOS in the pineal gland through beta-adrenergic receptors. To our knowledge, this represent the first demonstration of a regulation of NOS by a neurotransmitter in the CNS, as assayed under Vmax conditions.

Adrenergic Antagonists↗
PubMed1994

Pineal nitric oxide synthase: characteristics, adrenergic regulation and function.

Available studies indicate that the adrenergic stimulation of pineal cyclic GMP production involves stimulation of guanylyl cyclase activity by nitric oxide (NO) derived from arginine. This line of investigation was extended in the present study. Using a highly sensitive microassay, it was found that pineal NO synthase activity is present at levels approximately 30% of those in the cerebellum, that approximately 95% of enzyme activity is cytoplasmic, that the enzyme is Ca2+/calmodulin-dependent and that enzyme activity is inhibited by the arginine analog NG-nitro-L-arginine methyl ester (L-NAME). Norepinephrine treatment of intact glands in culture increased [3H]citrulline formation from [3H]arginine. This treatment also increased the formation of an NO-like compound, indicating that NO synthase activity in the intact gland is elevated by adrenergic stimulation. Studies on the effects of inhibition of NO synthase activity indicated that treatments known to inhibit NO synthase activity and the adrenergic stimulation of cyclic GMP accumulation did not inhibit adrenergic stimulation of pineal cyclic AMP, N-acetyltransferase activity or melatonin production. These observations support the hypothesis that NE stimulation of pineal cyclic GMP accumulation involves stimulation of a Ca2+/calmodulin-sensitive form of NO synthase, resulting in enhanced accumulation of NO; and, that although NO appears to play a role in the adrenergic stimulation of pineal cyclic GMP accumulation, it does not appear to play a critical role in the adrenergic stimulation of cyclic AMP, N-acetyltransferase activity or melatonin production.

Amino Acid Oxidoreductases↗
PubMed1994

Neurological complications from fat emulsion therapy.

Fat emulsion therapy is convenient for parenterally administering calories and essential fats. We report 2 children with neurological complications of fat emulsion therapy that arose before any systemic findings. The complications included focal and generalized seizures, weakness, and altered mental status. Biopsy and autopsy findings included cerebral endothelial and intravascular lipid deposition. Early recognition of fat emulsion therapy complications is essential as the neurological complications are potentially reversible with alteration of the parenteral diet.

Bone Marrow Transplantation↗
PubMed1994

Photoneural regulation of rat pineal nitric oxide synthase.

We report here a photoneural regulation of nitric oxide synthase (NOS) activity in the rat pineal gland. In the absence of the adrenergic stimulation following constant light exposure (LL) or denervation, pineal NOS activity is markedly reduced. A maximal drop is measured after 8 days in LL. When rats are housed back in normal light:dark (LD) conditions (12:12), pineal NOS activity returns to normal after 4 days. A partial decrease in pineal NOS activity is also observed when rats are placed for 8 days in LD 18:6 or shorter dark phases, indicating that pineal NOS activity reflects the length of the dark phase. Because it is known that norepinephrine (NE) is released at night from the nerve endings in the pineal gland and this release is blocked by exposure to light, our data suggest that NOS is controlled by adrenergic mechanisms. Our observation may also explain the lack of cyclic GMP response to NE observed in animals housed in constant light.

Amino Acid Oxidoreductases↗
PubMed1994

Changes in paired-pulse facilitation suggest presynaptic involvement in long-term potentiation.

Long-term potentiation (LTP) is a use-dependent form of synaptic plasticity that is of great interest as a potential cellular substrate underlying memory. It is important to determine the pre- and/or postsynaptic locus of LTP expression in order to study its underlying mechanisms. Despite intensive investigation, however, its locus of expression remains uncertain. It has been hypothesized that if LTP expression includes a presynaptic locus then it may alter the expression of another presynaptically mediated form of potentiation like paired-pulse facilitation (PPF), which is an increase in a second population excitatory postsynaptic potential when it is elicited shortly after a first. Previous authors have found no change in PPF in association with LTP. We re-examined the hypothesis, however, to reconcile the negative PPF data with other data that have suggested presynaptic involvement in LTP. Extracellular recordings were made in area CA1 of the rat hippocampal slice preparation. Surprisingly, PPF both increased and decreased significantly in association with LTP. The changes in PPF occurred in a predictable way, however. They correlated inversely with initial PPF magnitude so that a larger initial PPF was associated with a decrease in PPF with LTP while a smaller initial PPF was associated with an increase. Because PPF increased or decreased in individual slices in association with LTP, the average PPF of all slices did not change, in agreement with previous studies. The changes in PPF were also specific to LTP; that is, they were input specific, were not due to changes in inhibition or nonspecific effects of high-frequency stimulation, were not due to active postsynaptic currents or their nonlinear summation, and PPF changed with the same time course as LTP. We conclude that the mechanism of early LTP expression includes at least the presynaptic locus. Two hypotheses regarding the presynaptic mechanism underlying LTP expression, which are consistent with finding both increases and decreases in PPF with LTP, are (1) that there is an increase in the number of release sites with LTP or (2) that there is an increase in both the number of release sites and the probability of neurotransmitter release. Increases in the probability of neurotransmitter release alone would not appear to account for our findings since such increases have been associated only with decreases in PPF. Our findings do not exclude additional postsynaptic involvement.(ABSTRACT TRUNCATED AT 400 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1991

Contrast opacification of left ventricular myocardium following intravenous administration of sonicated albumin microspheres.

Albunex is a new echocardiographic (2-D echo) contrast agent that traverses the pulmonary vasculature when injected intravenously in humans. We examined whether intravenous Albunex resulted in changes in myocardial intensity of sufficient magnitude to produce time intensity curves (TICs). Thirty mildly hypertensive patients were divided into three groups of 10. Each patient received three injections of intravenous Albunex (group I dosages: 0.01, 0.02, and 0.04 cm3/kg; group II: 0.04, 0.06, and 0.08 cm3/kg; group III: 0.08, 0.1, and 0.12 cm3/kg) and two control injections of 5% human serum albumin while imaging with 2-D echo (phased-array; apical four-chamber). Fourty-three injections showed complete opacification of the left ventricle. Videointensity analysis of digitized end-diastolic frames produced myocardial TICs (total as well as background-subtracted intensity curves) in 20 of 43 injections. By visual inspection, a myocardial contrast effect was seen in 10 of 43 injections. Detection of myocardial TICs was dose-related (0 of 7 in group I, 9 of 18 in group II, 11 of 18 in group III) and always paralleled the degree of left ventricular opacification. No myocardial contrast effect was observed in any patient during control injections of albumin or in any patient in whom the injection of Albunex did not result in left ventricular opacification. Thus myocardial opacification with intravenous Albunex can be detected simultaneously with good left ventricular opacification. The potential significance of the myocardial opacification observed is discussed.

Adolescent↗
PubMed1988

Basal ganglia calcifications in a case of biotinidase deficiency.

Biotinidase deficiency leads to a biotin-deficient state, with cardinal symptoms of ataxia, alopecia, and skin rash presenting in infancy. Previous reports of head CTs in patients with biotinidase deficiency did not note basal ganglia calcifications. We report the first case of biotinidase deficiency with basal ganglia calcifications. There were no symptoms referable to basal ganglia dysfunction.

Amidohydrolases↗
PubMed1976

Inadequacy of information about drugs.

A questionary was sent back by 52 interns in three internal medicine services. It showed that approximately 60% of doctors lack "often" or "very often" pharmacological facts. Information about comparative efficacy is the most difficult to obtain.

Documentation↗