Search PubMed⌕ Search

Biomedical subjects

E Shapiro

Publications and source records attributed to E Shapiro.

At least 199 records · Page 11Linked to original sources
PubMed1987

Metabolites of arachidonic acid in the nervous system of Aplysia: possible mediators of synaptic modulation.

Release of arachidonic acid from membrane phospholipids is receptor-mediated and might generate second messengers in neurons. We tested this idea using the simple nervous system of the marine mollusk, Aplysia californica. Aplysia neural components metabolize arachidonic acid through lipoxygenase and cyclo-oxygenase pathways. We identified 2 major lipoxygenase products, 12- and 5-hydroxyeicosatetraenoic acids (12-HETE and 5-HETE), and 2 cyclo-oxygenase products, PGE2 and PGF2 alpha. These metabolites of arachidonic acid are formed in synaptosomes, as well as in identified nerve cell bodies, indicating that both lipoxygenase and cyclo-oxygenase pathways are active within neurons. Application of the modulatory neurotransmitter histamine to cerebral ganglia that had been labeled with 3H-arachidonic acid induced the formation of 3H-12-HETE. This response was inhibited by the histamine antagonist cimetidine. Furthermore, release of radioactive 5-HETE and 12-HETE was observed after intracellular stimulation of the histaminergic cell C2 in cerebral ganglia labeled with 3H-arachidonic acid. Cimetidine also inhibited this response. Application of serotonin or stimulation of the giant serotonergic cell (GCN) in the cerebral ganglion did not cause detectable amounts of the labeled eicosanoids to be released. We found that intracellular stimulation of putative histaminergic neurons in the L32 cluster of the abdominal ganglion, which produces presynaptic inhibition in L10 neurons, also elicited the release of 3H-12-HETE and 3H-PGE2. Thus, for the first time we provide evidence that synaptic stimulation promotes turnover of arachidonic acid in neurons. We suggest that metabolites of arachidonic acid are likely to participate in some postsynaptic responses to histamine and may be second messengers for presynaptic inhibition.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1986

Insulin stimulates renal glomerular sodium-potassium adenosine triphosphatase activity.

The effect of insulin on total and ouabain-inhibited membrane-bound adenosine triphosphatase (ATPase) activity in renal glomeruli isolated from adult white rats was examined. In concentrations of 1-10 micrograms/ml, insulin significantly stimulated the ouabain-inhibited (Na+ + K+)-ATPase activity, without affecting total (composite) ATPase activity. These results, coupled with previous findings demonstrating that glomerular (Na+ + K+)-ATPase activity is reduced in acute streptozotocin diabetes, suggest that the renal glomerulus is a target tissue with respect to this biologic effect of insulin.

Animals↗
PubMed1986

Biochemical and morphological correlates of transmitter type in C2, an identified histaminergic neuron in Aplysia.

There is compelling evidence that histamine serves as a neurotransmitter in C2, a pair of symmetrical neurons in the cerebral ganglion of Aplysia californica. These cells had previously been shown to contain high concentrations both of histamine and of its biosynthetic enzyme, histidine decarboxylase; in addition, 3H-histamine injected intrasomatically was found to move along C2's axons by fast transport. Furthermore, several actions of C2 on identified follower cells were simulated by the application of histamine. We have now characterized this identified neuron further. C2 converts 3H-histidine to histamine: 16% of the labeled precursor was converted to histamine 1 hour after intrasomatic injection. Synthesis of 3H-histamine is specific, since no conversion occurred after injection of other identified Aplysia neurons that are known to use other neurotransmitter substances. We also examined the fine structure of C2's cell body, axons, and axon terminals within the cerebral ganglion and in the nerves that carry its three peripheral branches, identified after injection of Lucifer Yellow, 3H-histamine, or horseradish peroxidase. Characteristic dense-core vesicles are present in all regions of the neuron, and are labeled after intrasomatic injection of 3H-histamine. These 100-nm vesicles together with 60-nm electron-lucent vesicles fill the varicose extensions of C2's neurites that are widely distributed within the ganglion, but only the smaller vesicles cluster at the membrane specializations presumed to be active zones that make contact with many neurons. The widespread distribution of axon terminals and varicosities is consistent with the idea that C2 is modulatory in function; 3H-histamine is taken up selectively by the cell body and axons of C2 and of several other putative histaminergic neurons in a Na+ -dependent manner. Characterization of these biochemical and morphological features of C2 adds to the large amount of information already available to make this identified cell a standard for identifying other neurons that use histamine as a transmitter.

Animals↗
PubMed1986

Hemi-inattention resulting from left hemisphere brain damage during infancy.

A case of right visual hemi-inattention is reported in a right-handed 14-year-old male who, as an infant, suffered a left hemisphere subdural hemorrhage and subsequently developed a large left posterior porencephalic cyst and right homonomous hemianopsia. Neuropsychological assessment reveals a significantly higher Verbal than Performance IQ, and evidence of hemi-inattention on tests of line bisection, picture matching from memory, and drawing figures from memory. Eye movement testing reveals poorer accuracy and latency of saccades for left-to-right eye movements than for right-to-left eye movements, but no appreciable difference in searching time for the left vs. the right visual spatial field. The findings are discussed in the context of developmental, educational, and rehabilitative implications with respect to the paucity of reports of visual hemi-inattention in children, and with consideration for effects unique to suffering a lesion in early infancy.

Adolescent↗
PubMed1986

Alpha 2 adrenergic receptors in hyperplastic human prostate: identification and characterization using [3H] rauwolscine.

[3H]Rauwolscine ([3H]Ra), a selective ligand for the alpha 2 adrenergic receptor, was used to identify and characterize alpha 2 adrenergic receptors in prostate glands of men with benign prostatic hyperplasia. Specific binding of [3H]Ra to prostatic tissue homogenates was rapid and readily reversible by addition of excess unlabelled phentolamine. Scatchard analysis of saturation experiments demonstrates a single, saturable class of high affinity binding sites (Bmax = 0.31 +/- 0.04 fmol./microgram. DNA, Kd = 0.9 +/- 0.11 nM.). The relative potency of alpha adrenergic drugs (clonidine, alpha-methylnorepinephrine and prazosin) in competing for [3H]Ra binding sites was consistent with the order predicted for an alpha 2 subtype. The role of alpha 2 adrenergic receptors in normal prostatic function and in men with bladder outlet obstruction secondary to BPH requires further investigation.

Binding, Competitive↗
PubMed1986

Effect of estrogens on the weight and muscarinic cholinergic receptor density of the rabbit bladder and urethra.

We have determined the muscarinic cholinergic receptor (MChR) density in the adult female rabbit bladder body and bladder base/urethra following three weeks of estrogen treatment. Fifteen female rabbits were separated into three treatment groups. Group I remained intact, Group II underwent bilateral ovariectomy, and Group III underwent simultaneous bilateral ovariectomy followed by subcutaneous placement of a 250 mg. estradiol pellet. The weight, total DNA content, and MChR density were determined for each of the tissues in the three treatment groups. The mean weight of the bladder body following ovariectomy and estrogen treatment (Group III) was three-fold greater than in the intact rabbits (Group I) (p less than 0.001) and two-fold greater than in the ovariectomized rabbits (Group II) (p less than 0.05). Similar increases were observed in the mean weights of the bladder base/urethral segments in the three treatment groups. The mean total DNA content in Group III was also significantly greater than Group I (p less than 0.01) and Group II (p less than 0.05) for both the bladder body and bladder base/urethral segment. The MChR density in the three treatment groups was determined using radioligand receptor binding using [3H]N-methylscopolamine ([3H]NMS). The MChR density in the bladder body (1.72 fmol./gm. DNA) for Group III was significantly decreased compared to the receptor density in both Group I (3.17 fmol./gm. DNA) and Group II (3.14 fmol./gm. DNA) (p less than 0.05). The binding of [3H] NMS to the MChR in bladder body was of high affinity (Kd = 0.07-0.15 nM) and was unaltered by hormonal treatment. No difference was found in the MChR density in the bladder base/urethral segment in any of the three treatment groups. In this study, we have shown that estrogens increase the weight and modulate the MChR density of the female rabbit bladder body. The ability to modulate neurotransmitter receptor density by sex steroid hormones may have important clinical implications.

Animals↗
PubMed1986

Calcium levels measured in a presynaptic neurone of Aplysia under conditions that modulate transmitter release.

We have utilized the Ca2+ indicator dye, Arsenazo III, to examine the role of presynaptic Ca2+ concentration in two types of synaptic plasticity observed at the synapses of cell L10 in Aplysia californica; post-tetanic potentiation (p.t.p. - the increased transmitter release which follows high frequency stimulation), and resting membrane potential modulation of release. Intracellular Ca2+ was monitored in the cell body and main neurites of L10 injected with Arsenazo III. Tetanic stimulation caused an increase in intracellular Ca2+ concentration that decayed, after tetanus, with fast and slow time constants which paralleled the time course of decay of p.t.p. When the voltage-sensitive Ca2+ current was reduced by removing external Ca2+ (0 mM-Ca2+, 4 mM-EGTA) or by blocking Ca2+ channels with divalent cation channel blocker (4 mM-Cd2+), tetanic stimulation did not cause increases in Arsenazo absorbance even when Na+ currents were not blocked. This finding suggests that Ca2+ entering the cell through voltage-dependent Ca2+ channels was the major source of Ca2+ which accumulated during the tetanus. Transmitter release is increased when L10 is maintained at a depolarized membrane potential, and is decreased when L10 is hyperpolarized. We found that the base-line Arsenazo absorbance signal in L10 increased when L10 was depolarized from -60 to -40 mV and decreased when L10 was hyperpolarized. This finding supports the idea that the steady-state Ca2+ concentration contributes to the membrane-potential modulation of transmitter release. These results support the idea that transmitter release can be modulated by the residual or resting Ca2+ concentration of the presynaptic cell.

Action Potentials↗
PubMed1986

Paroxysmal myoclonic dystonia with vocalisations: new entity or variant of preexisting syndromes?

From among 1377 patients with movement disorders, four patients had an unusual movement disorder characterised by paroxysmal bursts of involuntary, regular, repetitive, rhythmic, bilateral, coordinated, simultaneous, stereotypic myoclonus and vocalisations, often associated with tonic symptoms, interference with voluntary functioning, presence of hyperactivity, attention and learning disabilities, and resistance to treatment with haloperidol and other drugs. This symptom complex may represent a new disease entity, referred to here as paroxysmal myoclonic dystonia with vocalisations or a variant or combination of other movement disorders such as Gilles de la Tourette, myoclonic, or dystonic syndromes.

Adolescent↗
PubMed1986

Presynaptic inhibition produced by an identified presynaptic inhibitory neuron. I. Physiological mechanisms.

We have examined the synaptic conductance mechanisms underlying presynaptic inhibition in Aplysia californica in a circuit in which all the neural elements are identified cells (Fig. 1). L10 makes connections to identified follower cells (RB and left upper quadrant cells, L2-L6). These connections are presynaptically inhibited by stimulating cells of the L32 cluster (4). L32 cells produce a slow inhibitory synaptic potential on L10. This inhibitory synaptic potential is associated with an apparent increased membrane conductance in L10. Both the inhibitory postsynaptic potential (IPSP) and the conductance increase are voltage dependent; the IPSP could not be reversed by hyperpolarizing the membrane potentials to - 120 mV. The hyperpolarization of L10 induced by L32 reduces the transmitter output of L10 and thereby contributes to presynaptic inhibition. However, this hyperpolarization accounts for about 30% of the effect because presynaptic inhibition can still be observed even when the hyperpolarization of L10 by L32 is prevented by voltage clamping. When L10 is voltage clamped, stimulation of L32 produces a slow outward synaptic current associated with an apparent increased conductance. Both the synaptic current and conductance change measured under clamp are voltage dependent, and the outward current could not be reversed. This synaptic current is not mediated by an increase in C1- conductance. It is sensitive to external K+ concentration, especially at hyperpolarized membrane potentials. With L10 under voltage clamp, stimulation of L32 also reduces a slow inward current in L10. This current has time and voltage characteristics similar to those of the Ca2+ current. Presynaptic inhibition is still produced by L32 when L10 is voltage clamped, and transmitter release is elicited by depolarizing voltage-clamp pulses. This component of presynaptic inhibition, which accounts for approximately 70% of the inhibition, appears to be due to a decrease in the Ca2+ current in the presynaptic neuron.

Abdomen↗
PubMed1986

Presynaptic inhibition produced by an identified presynaptic inhibitory neuron. II. Presynaptic conductance changes caused by histamine.

We have examined the morphology and pharmacology of the L32 neurons, identified cells that mediate presynaptic inhibition in the Aplysia abdominal ganglion, to gain insight into the putative transmitter released by the L32 cells. We analyzed the fine structure of the synaptic release sites of L32 cells stained with horseradish peroxidase. Each varicosity of L32 was found to contain two general classes of vesicles. One class of vesicles is large (mean long diameter of 98 nm) and contains an electron-dense core that typically filled or nearly filled each vesicle profile. The second class of vesicles is smaller (mean long diameter of 67 nm) and relatively electron lucent. The size, distribution, and morphology of the vesicle population in L32's terminals was similar to that described at the synapses of the identified histaminergic neuron C2 in Aplysia (2). These morphological observations suggested that L32 cells might be histaminergic. Among the various putative transmitters tested, histamine was most effective in mimicking the postsynaptic effects of L32 cells onto L10, and onto other follower cells of L32 in the abdominal ganglion. Histamine also caused inhibition of transmitter output from L10. Both the IPSP produced by L32 in L10 and the response of L10 to histamine could be reversibly blocked by cimetidine, a histamine antagonist in Aplysia (14). These results support, but do not establish the identification of histamine as the putative transmitter of L32 cells. Histamine mimics the action of L32 in mediating presynaptic inhibition allowing us to examine in more detail the conductance changes in L10 underlying presynaptic inhibition. Voltage-clamp analysis revealed that histamine blocked the voltage-dependent Ca2+ current and increased a voltage-dependent K+ current in L10, much as did L32. Both of these changes are likely to act synergistically to inhibit transmitter release. Reduction of Ca2+ current in L10 would directly inhibit transmitter release from L10 directly by decreasing the amount of Ca2+ entering during spike depolarization. The increase in K+ current would act indirectly to reduce transmitter release from L10, by hyperpolarizing L10 and decreasing the amplitude and duration of spikes in L10, as well as reducing the steady-state Ca2+ influx. These results support the idea that in Aplysia presynaptic inhibition is caused primarily by a direct transmitter-mediated reduction in presynaptic Ca2+ current and secondarily by a hyperpolarization of the presynaptic neuron due to a transmitter-mediated increase in a K+ current.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdomen↗
PubMed1986

Patterns and predictors of home care use by the elderly when need is the sole basis for admission.

Data from the Manitoba Longitudinal Study on Aging is used to describe the 1975-78 home care utilization of a large probability sample of elderly interviewed in 1971. The predictors of home care use of these interviewees are identified by multiple logistic regression analysis. Findings indicate that a home care program based solely on professionally assessed need admits only a small minority of elderly and that, next to age, difficulty in coping with the instrumental activities of daily living is one of the best predictors of subsequent home care use. Differences between the determinants of home care and long-term institutional care are noted and the policy implications of the findings are discussed.

Activities of Daily Living↗
PubMed1986

Semiology, nosology and criteria for tic disorders.

Precise description of the signs, symptoms, classification and criteria for Tic Disorder and Gilles de la Tourette Syndrome (GTS) is important to reduce heterogeneity in studies and to develop hypotheses about the pathophysiology of these disorders. Previous diagnostic categories and criteria for Tic Disorders and GTS in DSM-III and ICD-9 were derived from our study of 114 consecutive patients, questionnaire responses by 31 patients and data on 76 patients from 8 published reports. During the past 20 years we have evaluated 1490 patients for movement disorders, of whom 1210 had GTS and 137 had another tic disorder. Analysis of these data and review of the literature serve as the basis for proposed revision of the signs, symptoms, nosology and criteria for Tic Disorders and GTS.

Compulsive Behavior↗
PubMed1986

Modulatory synaptic actions of an identified histaminergic neuron on the serotonergic metacerebral cell of Aplysia.

Possible sources of excitatory synaptic input to the serotonergic metacerebral cell (MCC) were determined by stimulating various neurons in the cerebral ganglion. Firing of the previously identified histaminergic neuron C2 was found to produce synaptic input to the MCC. The synaptic input consists of fast excitatory-inhibitory synaptic potentials on a background of a slow EPSP. The slow EPSP appears to be monosynaptic and chemically mediated since it persists in a solution of high divalent cations; broadening of the presynaptic spike enhances the EPSP; the size of the EPSP is a function of the Mg2+ and Ca2+ concentrations of the bathing solution; and the EPSP can be mimicked by application of histamine to the MCC. The slow EPSP, in addition to firing the MCC, can increase the excitability of the cell, even under conditions in which C2 is fired at a rate too slow to produce a measurable EPSP when the MCC is at rest potential. This property appears to be due to the fact that the slow EPSP results from an apparent decrease of membrane conductance so that the size of the EPSP increases markedly as the cell is depolarized, and the EPSP appears to be highly voltage-dependent so that it is small or absent close to the rest potential of the MCC. When the MCC is voltage-clamped, application of histamine to the bath results in an inward current that disappears when the MCC is hyperpolarized. The potential at which the histamine-induced current reverses or disappears is dependent on the concentration of external potassium, suggesting that, at least in part, the slow EPSP is due to a decrease of potassium conductance. The data on C2 are consistent with its being an element of the neuronal system that mediates a state of food arousal in Aplysia.

Animals↗
PubMed1985

Familial testicular cancer and urogenital developmental anomalies.

In a case-control study of testicular cancer, 6 of 269 cases (2.2%) reported a first-degree relative with testicular cancer, compared to 1 of 259 controls (0.4%). Fathers and brothers of testicular cancer cases had a six-fold elevated risk of developing a testicular malignancy compared to men in the general population. Cryptorchidism was reported in a first-degree relative in 1 (17%) of the familial cases versus 7 of 259 (2.7%) controls and 14 of 263 (5.3%) cases with a negative family history for testicular cancer. One half of the 6 familial cases reported a first-degree relative with a groin hernia (all surgically repaired before age 12), compared to 12.7% of 259 controls and 10.3% of 263 nonfamilial cases. Three familial clusters identified through the case-control study were selected for clinical evaluation. One of the 6 surviving males with testicular cancer in these 3 families had undergone orchiopexy and inguinal herniorrhaphy at age 6 years, and one had a hydrocele associated with his testicular tumor. Of the 12 living fathers and brothers of these 6 men, 3 reported childhood inguinal hernias, two with coexisting hydroceles. One additional hernia and two additional hydroceles were detected during urologic evaluation of these healthy relatives. The high prevalence of cryptorchidism, inguinal hernias, and hydroceles among men in these families suggests that an underlying alteration in urogenital embryogenesis may be associated with the familial predisposition to testicular neoplasia.

Adult↗
PubMed1985

Onset of androgen action in MCF-7 human breast cancer cells is not accompanied by receptor depletion.

Quantitative and qualitative changes in estrogen receptor follow addition of estradiol to estrogen responsive MCF-7 human breast cancer cells. We asked whether similar changes would accompany treatment of these cells with physiologically relevant concentrations of androgens. Androgen receptor sites were quantified by competitive protein binding assays on whole cells or extracts at various times following hormone addition. Both direct and exchange assays were employed. The androgen receptor in all of these experiments remained in a form which is completely exchangeable and approx 85% salt extractable. Quantity of receptor was unchanged (30,000 sites/cell, Kd 0.1 nM). Responsiveness to hormone treatment was demonstrated by antagonizing the estrogen dependent augmentation of cytoplasmic progesterone receptor in the MCF-7 cells with androgens. Thus, the androgen receptor was shown to be biologically active, but no time dependent quantitative or qualitative changes were observed during the first 6 h following androgen treatment.

Androgens↗