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M Segal

Publications and source records attributed to M Segal.

At least 217 records · Page 12Linked to original sources
PubMed1987

Ontogenesis of muscarinic receptors in cultured rat hippocampal cells.

The ontogeny of muscarinic cholinergic receptors was studied in primary cultures of dissociated rat hippocampal cells. The specific [3H]quinuclidinyl benzilate [( 3H]QNB) to intact cells was detected after two days in culture. Scatchard analysis revealed only a unique binding site at all of the days tested, with a very high affinity (0.205-0.253 nM) for the substrate. Specific binding kept increasing up to a level of 2035 fmol/mg protein after 15 days in culture. Protein content by itself also increased over time, reaching the highest level at 15 days (286 micrograms protein/35 mm plate). The cultured hippocampus can thus serve as a model system for the study of the development of muscarinic receptors in vitro.

Animals↗
PubMed1987

Interactions between grafted serotonin neurons and adult host rat hippocampus.

We have followed the development of physiological and functional properties of serotonin-containing raphe neurons grafted into an adult host hippocampus as a model system for graft-host interactions. These raphe cells have no clear identifying properties on the day of grafting: they develop them while growing in the host. Raphe neurons, recorded 1 month after grafting, possess adult normal physiological properties. These include high input resistance, slow membrane time constant, lack of inward rectification, a transient outward rectification, broad spikes having a Ca2+ component, lack of accommodation, and a large afterhyperpolarization. The graft is first innervated by host fibers and later projects to the host tissue. When stimulated, postsynaptic hyperpolarized responses are recorded in hippocampal neurons. In the freely moving rat, raphe grafts can restore sleep-wakefulness variations in an evoked population response of the hippocampus to afferent stimulation, which is eliminated by depletion of serotonin. These studies illustrate that grafted serotonin neurons develop functional relations with a host brain.

Animals↗
PubMed1987

Granulopoiesis in aged people: inverse correlation between bone marrow cellularity and myeloid progenitor cell numbers.

Results of a study on bone marrow (BM) cytology and cellularity, BM granulocytic-macrophage colony formation (GM-CFU-C), peripheral blood (PB) colony stimulating factor (CSF) and serum lysozyme activity in 20 elderly people aged from 64 to 89 are presented. Besides slight iron deficiency anemia, no hematological abnormality was detected. No change in PB and BM differential counts was found as compared to those obtained for normal adults. The BM cellularity and colony incidence were assessed using aliquots of the same specimen. GM-CFU-C frequency ranged from 15 to 156 (average 67.5) per 2 X 10(5) BM cells seeded. The largest number of colonies was observed in hypocellular BM samples (p less than 0.002). The level of serum lysozyme activity for the entire group was significantly higher than that obtained in healthy persons up to the age of 60 (p less than 0.001). The overall results support the notion that in old age, increased proliferation of committed granulopoietic stem cells in hypoplastic areas of the BM, assure normal numbers of mature blood cells in the periphery.

Aged↗
PubMed1987

Analysis of dose-response curves to methacholine. An approach suitable for population studies.

Dose-response curves to methacholine were examined in 9 normal and 10 asthmatic volunteers to determine whether the relationship between dose and response can be adequately summarized by means of a single, continuous measure that is not censored at lower levels of bronchial responsiveness. Subjects underwent a standard methacholine challenge test. There was a strong linear relationship between percent decline FEV1 and cumulative dose methacholine. We summarized each dose-response curve by the slope of a line extending from the origin to the last data point obtained. This summary dose-response slope effectively separated asthmatic from normal subjects, and there was a greater than 3,000-fold difference between the least and most responsive subjects. There was a high degree of correlation between the dose-response slope determined by the standard methacholine challenge protocol and that determined by an abbreviated protocol currently being used to examine nonspecific airway responsiveness in a large, longitudinal study of aging. Among the participants of the latter study, there is a unimodal, skewed distribution of dose-response slope. Dose-response slope is proposed as a quantitative measure of nonspecific airway responsiveness that avoids censoring and that may be particularly useful in epidemiologic studies.

Aging↗
PubMed1987

A case-control study of lung cancer and diesel exhaust exposure in railroad workers.

A case-control study of deaths among U.S. railroad workers was conducted to test the hypothesis that lung cancer is associated with exposure to diesel exhaust. Employed and retired male workers with greater than or equal to 10 yr of service who were born on or after January 1, 1900 and who died between March 1, 1981 and February 28, 1982 were eligible. We collected 87% of the death certificates from 15,059 deaths reported to the U.S. Railroad Retirement Board (RRB). Cases of lung cancer (1,256) were matched to controls by age (+/- 2.5 yr) and date of death (+/- 31 days). Potential exposure to diesel exhaust was assigned based on an industrial hygiene evaluation of jobs and work areas. Each subject's work history was determined from a yearly job report filed by his employer with the RRB from 1959 until death or retirement. Asbestos exposure prior to 1959 was categorized by the job held in 1959, the end of the steam locomotive era, or by the last job held if retirement occurred before 1959. Smoking histories were obtained by questionnaire from next of kin. Using multiple conditional logistic regression analysis to adjust for smoking and asbestos exposure, workers 64 yr of age or younger at the time of death with work in a diesel exhaust exposed job for 20 yr had a significantly increased relative odds (odds ratio = 1.41, 95% Cl = 1.06, 1.88) of lung cancer. No effect of diesel exhaust exposure was seen in workers 65 yr of age or older because many of these men retired shortly after the transition to diesel-powered locomotives.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1987

Leucovorin plus 5-fluorouracil: an effective treatment for metastatic colon cancer.

In Columbus, OH, 46 patients with measurable metastatic colorectal cancer were treated with leucovorin (LV) 80 mg/m2/20 h intravenous (IV) infusion followed by 5-fluorouracil (5-FU) 400 mg/m2 IV bolus daily for three days and then once weekly. Many patients had liver (62%) and/or multisite metastases (53%), carcinoembryonic antigen (CEA) greater than 10 (76%), documented tumor progression before entry (51%), and tumor-related symptoms (36%), but also good performance status (84%). Prior therapy consisted of radiotherapy (RT) in 18%, chemotherapy in 22%, both in 4%, and none in 56%. There were 36% objective responses and 31% stabilization, which we believe is a significant change in the natural history of these patients. Median survival was 8 months. Improved survival was seen in patients with single- rather than multiple-site involvement. Decreasing CEA levels were seen in 59% (always in responders or patients with stable disease), and correlated with longer survival time (11.0 v 5.5 months, P = 0.01). Palliation of tumor related symptoms occurred in 75%, with or without antitumor effect. One patient with prior RT died of neutropenic sepsis after only the three-day load, so we now recommend only weekly therapy in previously radiated patients. Otherwise, toxicity was mild, manifest as weakness in 62%, nausea in 53%, or diarrhea in 47%, which was the most common dose-limiting side effect. The occurrence or absence of toxicity did not predict outcome. Because of equivalent efficacy, mild toxicity, and less expense, this regimen should be considered for patients who desire therapy.

Adenocarcinoma↗
PubMed1987

AIDS education.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Stereochemical requirements for cannabimimetic activity.

The SAR of cannabimimetic activity in the cannabinoid series are reviewed with emphasis on the stereochemical requirements. Some new results are presented. The most important are that a, in humans, (-)-(1S)-delta-3-THC is much more active than (+)-(1R)-delta-3-THC; and b, with the 7-OH-delta-6-THC DMH enantiomers (32) and (33), the activity in several animal species resides completely in the (-)-(3R, 4R) enantiomer (32), the difference between the two enantiomers being up to several thousand times. The (3R,4R)-enantiomer (32) is much more active than delta-1- or delta-6-THC in animal tests, the exact level of activity depending on the test employed. The cannabimimetically inactive (+)-(3S,4S) enantiomer (33) was shown to be a potent analgetic in several animal tests. Thus, a complete dissociation between the cannabimimetic and the analgetic effects in a cannabinoid has been achieved, apparently for the first time.

Analgesics↗
PubMed1986

5,7-Dihydroxytryptamine modifies excitability of rat dorsal raphe serotonergic neurons in vitro.

Activity of serotonergic dorsal raphe neurons was recorded intracellularly in a brainstem slice preparation from rats before and after local microperfusion of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). The initial effect of the drug consisted of a transient hyperpolarization. Over 1-2 h after drug application there was a gradual decrease in efficacy of a hyperpolarizing current pulse to evoke a transient rectification. Also, action potentials in some cells failed to evoke a spike after-hyperpolarization. These effects are related to the neurodegenerative action of 5,7-DHT.

5,7-Dihydroxytryptamine↗
PubMed1986

Fetal raphe neurons grafted into the hippocampus develop normal adult physiological properties.

Embryonic midbrain raphe was grafted into serotonin-deficient adult rat hippocampus. Serotonin-containing neurons in the graft survive for at least 6 months after grafting. Grafted neurons develop physiological properties, not present on the day of grafting, identical to those of normal adult serotonin-containing neurons. These include (a) high input resistance and slow membrane time constant, (b) lack of inward rectification in response to hyperpolarizing current pulses and (c) a potent, 4-aminopyridine-sensitive transient outward rectification. The grafted neurons innervate the host tissue with axons that have a slow conduction velocity and refractoriness. It is suggested that grafted CNS neurons may possess normal physiological properties.

Animals↗
PubMed1986

Three types of low density lipoprotein receptor-deficient mutant have pleiotropic defects in the synthesis of N-linked, O-linked, and lipid-linked carbohydrate chains.

Biochemical, immunological, and genetic techniques were used to investigate the genetic defects in three types of low density lipoprotein (LDL) receptor-deficient hamster cells. The previously isolated ldlB, ldlC, and ldlD mutants all synthesized essentially normal amounts of a 125,000-D precursor form of the LDL receptor, but were unable to process this receptor to the mature form of 155,000 D. Instead, these mutants produced abnormally small, heterogeneous receptors that reached the cell surface but were rapidly degraded thereafter. The abnormal sizes of the LDL receptors in these cells were due to defective processing of the LDL receptor's N- and O-linked carbohydrate chains. Processing defects in these cells appeared to be general since the ldlB, ldlC, and ldlD mutants also showed defective glycosylation of a viral glycoprotein, alterations in glycolipid synthesis, and changes in resistance to several toxic lectins. Preliminary structural studies suggested that these cells had defects in multiple stages of the Golgi-associated processing reactions responsible for synthesis of glycolipids and in the N-linked and O-linked carbohydrate chains of glycoproteins. Comparisons between the ldl mutants and a large number of previously isolated CHO glycosylation defective mutants showed that the genetic defects in ldlB, ldlC, and ldlD cells were unique and that only very specific types of carbohydrate alteration could dramatically affect LDL receptor function.

Animals↗
PubMed1986

Properties of rat medial septal neurones recorded in vitro.

Activity of neurones of the rat medial septal nucleus (m.s.) was recorded in in vitro slice preparations. The recorded population could be divided into low (less than 30 M omega)- and high-input-resistance (greater than 30 M omega) neurones. The high-resistance neurones tended to fire spontaneous action potentials and post-synaptic potentials. Some of the spontaneously active cells fired rhythmically at rates of 2-10 Hz. The rhythmicity disappeared following hyperpolarization of the recorded cell. The cells could fire repetitive Ca2+ spikes in the presence of tetrodotoxin (TTX) and intracellular Cs+. Cd2+ blocked this rhythmicity. Most of the m.s. cells had a non-linear voltage-current relation in both the hyperpolarizing and depolarizing directions. Hyperpolarizing rectification was selectively blocked by extracellular Cs+ whereas depolarizing rectification could be blocked by TTX. A recovery from hyperpolarization was associated in many cells with a transient depolarization (anodal break (a.b.) potential). A 20 ms 15 mV hyperpolarization could trigger an a.b. potential. The a.b. potential was reduced by TTX and Cs+ but not by Cd2+ or Mn2+. Depolarization of quiescent neurones triggered action potential discharges. A common pattern of discharge was a burst of two spikes which kept a fairly constant interspike interval. The second spike in a doublet could not follow a rate of 10 Hz depolarizing current pulses. It was also sensitive to topical application of Cd2+. It is therefore suggested that Ca2+ might be involved in the generation of the doublet. Long depolarizing current pulses produced trains of action potentials, showing little accommodation and little after-hyperpolarization, indicating that these cells possess little Ca2+-dependent K+ current. Many cells emitted spontaneous post-synaptic potentials at high rates. These could be blocked by picrotoxin. Stimulation of the lateral septal (l.s.) nucleus produced a Cl-dependent i.p.s.p. The i.p.s.p. was blocked by picrotoxin. Topical application of gamma-aminobutyric acid (GABA) produced a marked Cl(-)-dependent increase in conductance. It is suggested that l.s. projects a GABA-mediated inhibitory connexion to the m.s. Acetylcholine (ACh) depolarized m.s. neurones and caused an increase in input resistance. The response was present in TTX or Cd2+-containing medium. Atropine blocked responses to ACh. 5-Hydroxytryptamine (5-HT) hyperpolarized m.s. neurones in a manner consistent with an increase in K+ conductance. The effects of 5-HT were seen in TTX- and Cd2+-treated m.s. slices.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

Rat hippocampal neurons in culture: Ca2+ and Ca2+-dependent K+ conductances.

Rat hippocampal neurons grown in dissociated cell culture were studied in a medium containing 1 microM tetrodotoxin (TTX) and 25 mM tetraethylammonium (TEA), which eliminated the Na+ and K+ conductances normally activated by depolarizing current injections. In this medium depolarizing current pulses evoked depolarizing regenerative potentials and afterhyperpolarizations in most cells. Both of these events were blocked by close application of Co2+ or Cd2+. These events resemble Ca2+ spikes reported previously in hippocampal pyramidal cells. The membrane potential at which these Ca2+ spikes could be triggered and the rheobase current necessary were dependent on the potential at which the cell was conditioned: the more depolarized the holding potential, the more negative the absolute potential at which a spike could be triggered and the less rheobase current required. The duration of these Ca2+ spikes was also sensitive to the holding potential: the more depolarized the holding level, the longer the duration of the triggered spikes. The amplitude and duration of the Ca2+ spikes were enhanced in a reversible manner by 0.5-1.0 mM 4-aminopyridine (4-AP) delivered in the vicinity of the cell. Two-electrode voltage-clamp analysis of cells studied in TTX, TEA-containing medium revealed an inward current response that peaked in 25-50 ms during depolarizing commands. This response first became detectable during commands to -30 mV. It peaked in amplitude during commands to -10 mV and was enhanced in medium containing elevated [Ca2+]0. It was blocked by either 20 mM Mg2+, 0.2 mM Cd2+, 5 mM Co2+, or 5 mM Mn2+. These results have led us to identify this inward current response as ICa2+. 4-AP enhanced the magnitude and duration of ICa2+ independent of the drug's depressant effects on a transient K+ current also observed under these same experimental conditions. In many but not all cells the Ca2+ spike was followed by a long-lasting hyperpolarization associated with an increase in membrane conductance. This was blocked by Co2+. Under voltage clamp ICa2+ was followed by a slowly developing outward current response that was attenuated by Co2+ or Cd2+. These properties observed under current- and voltage-clamp recording conditions are superficially similar to those previously reported for Ca2+-dependent K+ conductance mechanisms (IC) recorded in these and other membranes. Long-lasting tail currents following activation of IC inverted in the membrane potential range for the K+ equilibrium potential found in these cells.

4-Aminopyridine↗
PubMed1986

Voltage-clamp analysis of a Ca2+- and voltage-dependent chloride conductance in cultured mouse spinal neurons.

Current and voltage-clamp recordings were made at room temperature from cultured mouse spinal neurons using conventional two-electrode voltage-clamp techniques and electrodes filled with either 3 M KCl, 3 M CsCl, or 3 M Cs2SO4. In the presence of tetraethylammonium and tetrodotoxin, "fast" (rapidly rising and falling) action potentials (FAP) of variable duration were recorded in most neurons. "Slow" (slowly rising and falling) depolarizing potentials (SDP) occurred in 23% of the cells, when using KCl-filled electrodes, and in 82% of the cells with CsCl-filled electrodes. The SDP was frequently preceded by an FAP, although in some cells activation of the SDP occurred before the FAP threshold was reached and in a graded fashion. Both the FAP and SDP were abolished by Cd2+ and other Ca2+ antagonists. In cells exhibiting SDPs, voltage-clamp analysis revealed a sustained (noninactivating) inward current (Isin) during depolarizing steps to potentials more positive than -45 mV. Repolarizing steps resulted in slowly decaying inward tail currents (Itail). Both Isin and Itail were abolished in solutions nominally free of Cao2+, or containing Ca2+-channel antagonists. Bao2+ did not support Isin. The data indicated a U-shaped activation curve for Isin, peaking at about -10 mV. Activation of Isin occurred exponentially with a time constant of approximately 140 ms at -23 mV, becoming faster at more depolarized potentials (ca. 50 ms at -2 mV). Deactivation was slow, giving rise to tail currents lasting seconds. In some cases deactivation could be described by a single exponential process, although frequently the kinetics were more complex. Deactivation was faster at hyperpolarized potentials and sensitive to extracellular ([Ca2+]o), duration of activating voltage steps, and the degree of activation of Isin. Using CsCl-filled electrodes, the reversal potential (Erev) for Isin was -1.7 mV (SEM 3.5 mV, n = 20). Erev always corresponded to the reversal potential for gamma-aminobutyric acid-evoked currents in the same cell. In experiments in which Cs2SO4-filled electrodes were used, Erev was estimated to be -44 mV (SEM 2.3 mV, n = 9). Neither complete substitution of Nao+ with choline ions nor elevation of [K+]o 10-fold significantly affected the estimated Erev. However, substitution of Cl0- with isethionate or methanesulphonate increased the amplitude of inward currents (recorded with CsCl-filled electrodes) and shifted Erev to more depolarized potentials. The results indicate that Cl- are the primary charge carriers for this current and that Cai2+ is required for its activation, leading us to identify it as ICl(Ca).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Coexistence of sporadic multiple endocrine neoplasia and scapular ectopic breast. Coincidence or biologically associated?

We describe a patient who presented with sporadic pheochromocytoma and parathyroid adenoma in the absence of medullary thyroid carcinoma, which coexisted with fully developed scapular ectopic breast tissue. If not coincidental, this association might support the concept that all components of multiple endocrine neoplasia type IIA originate from embryonic ectodermal tissue, and that sporadic multiple endocrine neoplasia type IIA, as well as ectopic breast tissue, may result from a noxious event at a critical embryonic stage.

Adenoma↗