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M S Levine

Publications and source records attributed to M S Levine.

At least 19 recordsLinked to original sources
PubMed1999

Metabotropic glutamate receptor modulation of excitotoxicity in the neostriatum: role of calcium channels.

We have previously shown that metabotropic glutamate receptor (mGluR) activation can attenuate N-methyl-d-aspartate (NMDA)-induced excitotoxic injury in the neostriatum both in vivo and in vitro. Our earlier studies made use of the non-subtype selective mGluR agonist 1-amino-cyclopentane-1,3-dicarboxylic acid (tACPD). In the present study, we extended these observations by identifying the subtype of mGluR involved. Using selective mGluR agonists, we provide evidence that the Group II mGluRs are responsible for inhibition of NMDA excitotoxicity in the neostriatum. In addition, we provide evidence that the inhibitory effects of tACPD on excitotoxicity are dependent upon calcium influx as they are blocked by a low calcium solution as well as the broad-spectrum calcium channel blocker cadmium. The tACPD-induced attenuation was also blocked by omega-conotoxin GVIA suggesting participation of N-type calcium channels. Whole cell voltage clamp recordings were made to directly determine the effects of mGluRs on voltage-gated calcium channels in neostriatal neurons. As predicted, both tACPD and the Group II agonist 3C4HPG inhibited calcium currents in neostriatal neurons. Again this effect was blocked by omega-conotoxin GVIA. Overall the results suggest that mGluR regulation of voltage-gated calcium channels can limit NMDA toxicity in the neostriatum.

Animals↗
PubMed1999

Cortical damage enhances pemoline-induced self-injurious behavior in prepubertal rats.

Self-injurious behavior (SIB) is a devastating characteristic of several developmental disorders including a number of mental retardation syndromes. The functional neuroanatomy and neuropharmacology of SIB is not well understood. Self-biting behavior (SBB) can be induced in rats by a high dose, systemic injection of pemoline (250 mg/kg, SC). This animal model allows for the investigation of anatomical and pharmacological aspects of SIB. Cortical pathology is a common occurrence in human disorders with SIB, and may be a fundamental pathological factor in producing the behavior. The present experiment was designed to investigate the effects of cortical damage on pemoline-induced SBB in prepubertal rats. Bilateral cortical aspirations were performed in 3-5-week-old rats. One week postsurgery, a pemoline challenge was administered. Behavioral comparisons were completed between the lesion group and an anesthetized-only control group. Results indicated that cortical damage significantly enhanced pemoline-induced SBB, along with some of the other pemoline-induced stereotypical behaviors. These results support the hypothesis that cortical damage influences the expression of stimulant-induced self-injury, and potential mechanisms for this influence are suggested.

Animals↗
PubMed1999

Gastrointestinal imaging: a systems analysis comparing digital and conventional techniques.

OBJECTIVE: The purpose of this study was to compare digital and conventional methods of gastrointestinal imaging based on the cost of image storage and estimated overall costs, radiation exposure to the patient, and duration of the examination. MATERIALS AND METHODS: Our study sample consisted of 128 patients who underwent conventional gastrointestinal studies (64 double-contrast upper gastrointestinal examinations and 64 double-contrast barium enemas) and 139 patients who underwent digital gastrointestinal studies (66 double-contrast upper gastrointestinal examinations and 73 double-contrast barium enemas). The number of images and films for each study was recorded, and the mean cost of image storage and the estimated overall costs for digital versus conventional studies were calculated. Both the duration of fluoroscopy and the time from start to completion of the study were obtained from our radiology information system. From these data, we calculated mean radiation exposure to the patient and the duration of the examination. Finally, referring physicians completed a questionnaire about their level of satisfaction with paper prints generated from digital gastrointestinal studies. RESULTS: When digital studies were compared with conventional studies, the mean cost of image storage decreased by 45% and the estimated overall 10-year costs decreased by 8%. The mean number of spot images increased by 8% for upper gastrointestinal examinations and by 25% for barium enema examinations, whereas the mean duration of fluoroscopy decreased by 4% and by 10%, respectively. As a result, radiation exposure to patients increased by only 2%, a difference that did not approach statistical significance. Finally, the mean duration of examinations decreased by 24% for upper gastrointestinal examinations and by 33% for barium enemas. Approximately 85% of the physicians who completed the questionnaires indicated that they reviewed the paper prints generated from digital studies and that they would like to continue receiving them. CONCLUSION: Digital gastrointestinal imaging systems are associated with higher initial costs than conventional systems, but the long-term costs of these digital imaging systems are slightly less because of the lower cost of image storage, and radiation exposure to patients is comparable. The shorter duration of digital examinations is a potential benefit of this technology, allowing improved patient throughput. Finally, referring physicians have a high level of satisfaction with paper prints generated from digital imaging.

Attitude of Health Personnel↗
PubMed1998

Value of digital fluoroscopy for the diagnosis of pneumatosis coli.

Two cases are presented of benign pneumatosis coli diagnosed on digital fluoroscopic barium enema examinations, in which the gas-filled cysts in the colonic wall were only recognized by postprocessing of the images (i.e. increasing the brightness and contrast settings) at the computer workstation. When digital barium enemas are performed, we therefore recommend image postprocessing to evaluate polypoid lesions in order to differentiate pneumatosis coli from true colonic neoplasms.

Aged↗
PubMed1998

Action sequencing is impaired in D1A-deficient mutant mice.

The role of dopamine in the production of behaviour is multifarious in that it can influence different aspects of movement (e.g. movement initiation, sensorimotor integration, and movement sequencing). A characteristic of the dopamine system which seems to be critical for the expression of this diverse influence is its varied receptor population. Previous studies have shown that specific receptor subtype activation leads to specific behavioural responses or alterations of selective aspects of movement. It is known that one of the important influences of dopamine includes sequential co-ordination of 'syntactic' patterns of grooming movements because moderate loss of the dopaminergic nigrostriatal projections specifically disrupts these patterns without affecting grooming actions in a general fashion (Berridge, K.C. Psychobiology, 15, 336, 1989). The specific receptors of the dopamine family which play a key part in this co-ordination of movement sequences is not known. In the present study, we examined the serial order of particular syntactic sequences or chains of grooming actions in mice lacking D1A receptors to explore the relationship between this receptor subtype and movement sequencing. Mutant mice had shorter grooming bouts and a disruption of the organization of sequential patterns compared with wild-type littermate controls. Sequential disruption was reflected in the failure of D1A mutants to follow the syntactic pattern of grooming to completion. This sequential disruption deficit appeared to be specific, as mutant mice initiated more syntactic chains than wild-type controls even though they were less likely to complete them. These results support the hypothesis that D1A receptor activation plays a part in the sequencing of natural action. This conclusion has important implications for the understanding of the functional heterogeneity of dopamine receptor subtypes and of the aetiology of symptoms observed in patients with basal ganglia disease.

Animals↗
PubMed1998

Dopaminergic modulation of early signs of excitotoxicity in visualized rat neostriatal neurons.

Cell swelling induced by activation of excitatory amino acid receptors is presumably the first step in a toxic cascade that may ultimately lead to cell death. Previously we showed that bath application of N-methyl-D-aspartate (NMDA) or kainate (KA) produces swelling of neostriatal cells. The present experiments examined modulation of NMDA and KA-induced cell swelling by dopamine (DA) and its receptor agonists. Nomarski optics and infra-red videomicroscopy were utilized to visualize neostriatal medium-sized neurons in thick slices from rat pups (12-18 postnatal days). Increase in somatic cross-sectional area served as the indicator of swelling induced by bath application of glutamate receptor agonists. NMDA induced cell swelling in a dose-dependent manner. Activation of DA receptors in the absence of NMDA did not produce swelling. DA and the D1 receptor agonist SKF 38393, increased the magnitude of swelling produced by NMDA. This effect was reduced in the presence of the D1 receptor antagonist, SCH 23390. In contrast, activation of D2 receptors by quinpirole decreased the magnitude of NMDA-induced cell swelling. DA slightly attenuated cell swelling induced by activation of KA receptors. Quinpirole produced a significant concentration-dependent reduction in KA-induced swelling while SKF38393 increased KA-induced swelling, but only at a low concentration of KA. Together, these results provide additional support for the hypothesis that the direction of DA modulation depends on the glutamate receptor subtype, as well as the DA receptor subtype activated. One possible consequence of these observations is that endogenous DA may be an important contributing factor in the mechanisms of cell death in Huntington's disease.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1998

Glutaraldehyde-induced esophageal injury. Histologic study of laboratory rats.

RATIONALE AND OBJECTIVES: A patient was encountered with a long esophageal stricture that may have been caused by glutaraldehyde-contaminated endoscopic equipment. An in vivo study of laboratory rats was performed to determine the effect of glutaraldehyde exposure on the esophagus. METHODS: Ten laboratory rats were divided into five groups that received daily gavage of the esophagus with either 3.2% glutaraldehyde solution (treated rats) or 1 mL of normal saline (control rats) for varying durations. After the rats were killed, histologic sections from the esophagus were reviewed in a blind fashion. The degree of inflammatory infiltrate at the gastroesophageal junction was quantified as mild, moderate, or marked. RESULTS: Histologic examination revealed greater neutrophilic infiltration in the submucosa of the gastroesophageal junction in three of four glutaraldehyde-treated rats compared with controls. Treated rats also had evidence of segmental esophageal vasculitis not seen in any of the controls. Both controls and treated rats had areas of myositis and myonecrosis within the esophagus. CONCLUSION: Exposure to glutaraldehyde has a toxic effect on the rat esophagus. Glutaraldehyde-induced esophageal injury should therefore be considered in patients who develop esophagitis or esophageal strictures after upper endoscopy.

Animals↗
PubMed1998

Gastric mucosa-associated lymphoid tissue lymphoma: radiographic findings in six patients.

PURPOSE: To determine the radiographic findings of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma on double-contrast upper gastrointestinal studies. MATERIALS AND METHODS: Pathology records, double-contrast upper gastrointestinal studies, and medical records of six patients with gastric MALT lymphoma were retrospectively reviewed. RESULTS: The most common clinical findings at presentation included epigastric pain (n = 6), dyspepsia (n = 4), and nausea and vomiting (n = 4). Double-contrast studies revealed rounded, often confluent nodules of varying size in four patients with low-grade MALT lymphoma. Nodularity was located in the gastric antrum (n = 2), body (n = 1), or body and fundus (n = 1). A fifth patient had a malignant-appearing 1-cm-diameter antral ulcer, and a sixth had a 10-cm-diameter polypoid, ulcerated mass in the gastric fundus. The latter patient was found to have high-grade MALT lymphoma with low-grade MALT lymphoma abutting the tumor. Five patients had associated Helicobacter pylori gastritis. Five patients had stage I disease, and one had stage IIB disease. At endoscopic follow-up (n = 4), marked regression of tumor occurred after treatment with antibiotics, chemotherapy, and/or radiation therapy. CONCLUSION: When low-grade MALT lymphoma is suspected on the basis of barium study results, endoscopic biopsy specimens should be obtained for a definitive diagnosis so these patients can be treated before the development of high-grade gastric lymphoma.

Aged↗
PubMed1998

Primary malignant melanoma of the esophagus: radiographic findings in seven patients.

PURPOSE: To evaluate the radiographic findings in a series of patients with primary malignant melanoma of the esophagus. MATERIALS AND METHODS: Seven cases of primary esophageal melanoma were collected from the Hospital of the University of Pennsylvania and the radiologic archives of the Armed Forces Institute of Pathology. All patients underwent esophagography (double-contrast esophagograms in four patients, single-contrast esophagograms in three patients). Medical, endoscopic, and pathology reports were also reviewed. RESULTS: Six patients presented with dysphagia (average duration, 5 months). The remaining patient had recent onset of melena. In all patients, barium studies revealed bulky, polypoid intraluminal masses that focally expanded the esophagus without causing obstruction. The tumors were located in the distal third of the thoracic esophagus in four patients, the middle third in two, and the proximal third in one. Tumor pigmentation was noted at endoscopy in only one patient. All patients underwent extensive esophageal resection. Of four patients with clinical follow-up findings, two were alive and well 2 and 6 months after surgery; the other two had metastases to the lung and liver within 2 months of surgery. CONCLUSION: Primary esophageal melanomas have strikingly similar barium study findings, appearing as bulky, polypoid intraluminal masses that focally expand the esophagus without causing obstruction. Despite its rarity, primary esophageal melanoma should be considered when characteristic findings are present on barium studies.

Esophageal Neoplasms↗
PubMed1998

Dopaminergic modulation of NMDA-induced whole cell currents in neostriatal neurons in slices: contribution of calcium conductances.

The present experiments were designed to examine dopamine (DA) modulation of whole cell currents mediated by activation of N-methyl-D-aspartate (NMDA) receptors in visualized neostriatal neurons in slices. First, we assessed the ability of DA, D1 and D2 receptor agonists to modulate membrane currents induced by activation of NMDA receptors. The results of these experiments demonstrated that DA potentiated NMDA-induced currents in medium-sized neostriatal neurons. Potentiation of NMDA currents occurred at three different holding potentials, although it was more pronounced at -30 mV. It was mediated by D1 receptors, because it was mimicked by D1 agonists and blocked by exposure to a D1 antagonist. Activation of D2 receptors produced inconsistent effects on NMDA-induced membrane currents. Either decreases, increases, or no effects on NMDA currents occurred. Second, we examined the contributions of intrinsic, voltage-dependent conductances to DA potentiation of NMDA currents. Blockade of K+ conductances did not prevent DA enhancement of NMDA currents. However, voltage-activated Ca2+ conductances provided a major contribution to DA modulation. The dihydropyridine L-type Ca2+ channel blockers, nifedipine, and methoxyverapamil (D-600), markedly reduced but did not totally eliminate the ability of DA to modulate NMDA currents. The D1 receptor agonist SKF 38393 also enhanced Ba2+ currents in neostriatal neurons. Together, these findings provide evidence for a complex interplay between DA, NMDA receptor activation and dihydropyridine-sensitive Ca2+ conductances in controlling responsiveness of neostriatal medium-sized neurons.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1998

Dopamine and N-methyl-D-aspartate receptor interactions in the neostriatum.

This review examines dopamine (DA) and glutamate receptor interactions in the neostriatum (NS) primarily from a neurophysiological perspective. Historically, a clear understanding of the function of DA in the NS has been difficult because it was considered a classical neurotransmitter with either excitatory or inhibitory actions and because many of the data were obtained by use of varying methodologies. When DA is considered a neuromodulator whose role is to alter how NS cells respond to glutamatergic inputs, many of its actions can be accounted for and predicted with great accuracy within a model of receptor subtype. In this model, DA via activation of D1 receptors potentiates responses mediated by activation of N-methyl-D-aspartate (NMDA) receptors. DA via activation of D2 receptors attenuates responses mediated by activation of non-NMDA receptors. Outcomes of combinations of NMDA and D2 and non-NMDA and D1 receptors are not as predictable. The mechanisms underlying the D1-NMDA receptor interactions appear to involve alterations in cell excitability mediated by activation of Ca2+ conductances and/or phosphorylation of NMDA receptors. Less is known about mechanisms underlying the D2-non-NMDA receptor interaction. The functional implications of this model in setting membrane potentials, signal-to-noise ratio, plasticity and excitotoxicity are discussed.

Afferent Pathways↗
PubMed1998

Postnatal development of glutamate receptor-mediated responses in the neostriatum.

Three experimental approaches were used to examine the maturation of N-methyl-D-aspartate (NMDA) receptors in the neostriatum and compare their developmental profile to that of the non-NMDA receptors [alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate (KA)]. The first, and least conventional approach utilized infrared videomicroscopy to measure NMDA-induced swelling in single cells in a brain slice. The results demonstrated that NMDA receptors display an incremental pattern of postnatal development with no responses at postnatal day (PND) 3, weak responses at PND 7, the largest responses by PND 14 and slight decreases at PNDs 21 and 28. At PNDs 3 and 7, KA-induced cell swelling was proportionately greater than NMDA-induced cell swelling suggesting earlier maturation of this non-NMDA receptor subtype. The second approach used whole-cell patch clamp analysis to examine NMDA currents and compare their maturation to AMPA/KA-induced currents. Though the data are still preliminary, a very similar developmental pattern emerged. NMDA-induced currents were small and developed slowly after PND 7. In contrast, AMPA/KA-induced currents were larger and appeared to develop earlier. Finally, dizocilpine (MK-801) binding was measured in homogenates of neostriatal tissue. The ontogeny of binding resembled a step function with increases between PNDs 3 and 7 and PNDs 14 and 21. Binding peaked at PND 28 and then declined slightly in the adult (PND 60). The affinity of MK-801 for the receptor did not change during postnatal development. These findings demonstrate the pattern of functional development of glutamate receptors in the neostriatum. The NMDA receptor subtype displays minimal functional development until PND 14. In contrast, neostriatal AMPA/KA receptor function appears to precede NMDA receptor function.

Aging↗
PubMed1998

Striatal excitatory amino acid receptor subunit expression in the D1A-dopamine receptor-deficient mouse.

The influence of dopamine receptor deletion on the expression and distribution of striatal excitatory amino acid (EAA) receptor subunits comprising the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtypes were examined in the D1A dopamine (DA) receptor-deficient mouse. EAA receptor subunit immunofluorescent staining was altered by the DA receptor genetic mutation. The NMDA-R1 subunit was used as a marker for NMDA-type receptors. The number of striatal neurons expressing this subunit decreased and there was a modest attenuation in the neuropil staining in the mutants in contrast to littermate controls. The R1 subunit for the glutamate receptor (GluR1) was used as an indicator of the AMPA receptor subtype. Immunostaining for this subunit also showed changes induced by deletion of the DA receptor subtype. In contrast to the NMDA-R1 subunit, neuropil staining for the GluR1 subunit was elevated in the mutant in comparison to littermate controls, such that the immunofluorescent reaction obscured detection of the subunit protein in striatal interneurons. The results are discussed in relation to the potential impact on functional interactions between the EAA and DA systems in the striatum.

Animals↗