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S M Pulst

Publications and source records attributed to S M Pulst.

101 records · Page 6Linked to original sources

The Alzheimer amyloid precursor protein maps to human chromosome 21 bands q21.105-q21.05.

The Alzheimer amyloid protein precursor (APP) has previously been localized to human chromosome 21q11.2-q21. We have refined the regional localization to a small region including chromosome bands 21q21.105-q21.05 by using quantitative Southern blot analysis of cell lines aneuploid for parts of chromosome 21. Our findings exclude the APP gene from the minimal region producing the classical phenotypic features of Down syndrome. This further narrowing of the APP location will help in identifying the physical location of the gene causing familial Alzheimer disease.

Amyloid↗

Neuroendocrine bag cells of Aplysia are activated by bag cell peptide-containing neurons in the pleural ganglion.

1. The generation of egg-laying behavior in the marine mollusk Aplysia involves a prolonged burst discharge in the neuroendocrine bag cells, which secrete neuropeptides derived from the egg-laying hormone/bag cell peptide (ELH/BCP) precursor protein. 2. Besides the bag cells, which are located in the abdominal ganglion, small clusters of neurons in the cerebral and pleural ganglia also express the ELH/BCP neuropeptides. We made intracellular recordings from 32 of these ELH/BCP cells in right pleural ganglia, in 18 preparations, to characterize their physiological properties and their functional relationship to the bag cells. 3. The identification of these ELH/BCP cells was confirmed by pressure injection of Lucifer yellow and subsequent immunocytochemical processing for alpha-BCP immunoreactivity. 4. The basic electrophysiological properties of the pleural ELH/BCP cells were similar to those of the bag cells. These pleural cells were directly demonstrated to be electrically coupled, and direct intracellular stimulation of individual pleural ELH/BCP cells initiated prolonged, synchronous burst discharges in the entire cluster through a positive feedback mechanism. 5. Burst discharges elicited in the pleural ELH/BCP cells consistently initiated burst discharges in the bag cells. Bag cell burst discharges were less effective in initiating burst discharges in the pleural ELH/BCP cells, indicating that there were reciprocal but asymmetrical connections. 6. The results show that the pleural ELH/BCP cells are functionally coupled to the bag cells. They support the hypothesis that the pleural ELH/BCP cells are part of the descending pathway that initiates bag cell activity and egg-laying behavior, in vivo.

Action Potentials↗

Immunostaining for peptides of the egg-laying hormone/bag cell peptide precursor protein in the head ganglia of Aplysia.

Egg-laying hormone and alpha-bag cell peptide are two neuropeptides derived from a common precursor protein in the marine mollusk Aplysia. Previous studies indicate that they are neurotransmitters that co-exist in individual bag cell neurons and most bag cell processes in the abdominal ganglion. In the present investigation we used double-label immunocytochemistry with highly specific antisera to describe their distribution elsewhere in the CNS. We found that a small cluster of cells and their fibers in the pleural ganglion that were previously described as being immunoreactive for egg-laying hormone were also immunoreactive for alpha-bag cell peptide(1-9). A previously described group of small cell bodies in the cerebral ganglion also stained for both peptides. However, the fiber arborizations located near them were immunoreactive for alpha-bag cell peptide(1-9), but not egg-laying hormone. This suggests that there is alternative processing of the precursor protein or differential transport of the peptides from the cell bodies. The specificities of the antibodies indicate that all of the neurons that stain for egg-laying hormone-like peptides in the CNS synthesize peptides derived from the egg-laying hormone/bag cell peptide precursor, rather than peptides derived from other members of the egg-laying hormone gene family. They also suggest that peptides derived from the related A or B precursor proteins are not synthesized in the CNS, or at levels too low to detect. The results are consistent with the proposal that the behavior associated with egg-laying is initiated and controlled by peptide transmitters derived from a single gene and expressed in specific neurons of the CNS.

Animals↗

Presence of immunoreactive alpha-bag cell peptide[1-8] in bag cell neurons of Aplysia suggests novel carboxypeptidase processing of neuropeptides.

alpha-bag cell peptide (alpha BCP) is a putative neurotransmitter released from bag cell neurons of the marine mollusc Aplysia. alpha BCP is present in bag cell extracts and releasate from bag cells in two neuroactive forms: alpha BCP[1-9] and alpha BCP[1-8]. alpha BCP[1-8] is 30 times as potent as [1-9] in inhibiting target neurons, suggesting that both forms of the peptide serve as neurotransmitters. However, biochemical and molecular genetic data suggest that only alpha BCP[1-9] is originally cleaved directly from a larger precursor protein and that generation of alpha BCP[1-8] would require an unusual C-terminal leucine cleavage of alpha BCP[1-9]. To further ascertain which forms of alpha BCP are normally present in bag cells, we generated highly specific antisera to each peptide. We found intense immunostaining for both peptides in bag cell somata and nerve terminals. Moreover, both forms were stable in bag cell extract for at least 1 hr, which suggests that proteolysis in the extracts had been effectively inhibited. These results suggest that both alpha BCP[1-8] and [1-9] are normally present in bag cell somata and terminals and that a small amount of alpha BCP[1-9] is processed to alpha BCP[1-8] in vesicles before release. The results support the interpretation that the activity of an intravesicular carboxypeptidase generates alpha BCP[1-8] and thereby regulates the amount of inhibitory activity released during a bag cell discharge.

Animals↗

Coexistence of egg-laying hormone and alpha-bag cell peptide in bag cell neurons of Aplysia indicates that they are a peptidergic multitransmitter system.

Double-label immunocytochemistry reveals that immunoreactivity for two putative peptide transmitters, egg-laying hormone and alpha-bag cell peptide, co-exist in most bag cell somata and processes in the abdominal ganglion of the marine mollusc Aplysia. Together with previous physiological and biochemical data these findings indicate that the neuroendocrine bag cells are a multitransmitter system which utilizes two or more peptides derived from a common precursor.

Animals↗

Carbon monoxide poisoning with features of Gilles de la Tourette's syndrome.

A previously healthy 58-year-old man had severe carbon monoxide poisoning. Following a comatose state, tics of the head, coprolalia, fits of shouting, and abnormal vocal utterances developed. In addition to the signs of diffuse encephalopathy, he had some of the features associated with idiopathic Gilles de la Tourette's syndrome. The computed tomographic scan showed ventricular enlargement and low-density areas in the basal ganglia.

Brain↗

External ophthalmoplegia, alpha and spindle coma in imipramine overdose: case report and review of the literature.

A 13-year-old boy with imipramine overdose developed seizures, respiratory arrest, and coma. Abnormalities of oculovestibular reflexes, electroencephalograms, and brainstem auditory evoked potentials were monitored in relation to measurements of drug levels. An alpha-coma electroencephalographic pattern evolved into one evidencing spindle coma and eventually into a normal pattern. Prolonged brainstem auditory evoked potentials also normalized as coma and oculocephalic reflex abnormalities resolved. In spite of the history that suggested hypoxic damage, the absence of reflex eye movements in a comatose patient and the presence of alpha- and spindle-coma electroencephalographic patterns, even with prolonged brainstem auditory evoked potentials, are not reliable prognostic indicators in tricyclic drug overdose.

Adolescent↗

Thermographic assessment of impaired sympathetic function in peripheral nerve injuries.

Twenty-three patients with focal, strictly unilateral lesions of the peripheral nervous system were examined by infrared-thermography. The Minor sweat test was used to determine if sympathetic outflow was disturbed. In fifteen patients without a concomitant sympathetic lesion (controls) thermosymmetry was not disturbed. Eight patients had evidence of abnormal sweat secretion. In these patients thermoregulation was severely disturbed. During the first 5 to 8 months, affected skin areas were hyperthermic, whereas later only hypothermia was observed. Cold stimuli increased temperature differences in patients with disturbed sympathetic function, but not in controls. Thermography is a reliable, non-invasive technique to detect a lesion of sympathetic outflow and permits an estimation of the time-course of the lesion.

Adolescent↗

Potentiation of BCNU-induced cytotoxicity and sister chromatid exchanges by dibromodulcitol in vitro.

Dibromodulcitol (DBD) is an anticancer agent that is cytotoxic against animal and human brain tumors in vivo. Clinical trials of combination therapy with radiation, DBD, and a nitrosourea have shown some efficacy, but the mechanisms that lead to enhanced cytotoxicity are poorly understood. We investigated the effects of pretreatment with DBD on cell survival and sister chromatid exchange (SCE) caused by subsequent treatment with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) in 9L rat brain tumor cells. Pretreatment of 9L cells for 24 hr with 5 microM DBD potentiated the cell kill produced by a 1-hr treatment with BCNU; the dose enhancement ratio was 1.7 at the 10% survival level. Treatment of 9L cells for 24 hr with 1 microM DBD induced 39 +/- 12 SCEs/metaphase. There was a 50-75% increase in BCNU-induced SCEs, compared with BCNU alone, after a 24 hr pretreatment with DBD. Thus DBD potentiation of BCNU cytotoxicity appears to be related to increased DNA damage.

Animals↗