Antitumor monoclonal antibodies generated by immunization with mucins.

This report describes the development and characterization of monoclonal antibody EG2.3. Although produced from a fusion that used splenocytes from donor mice immune to bovine salivary mucin (BSM), EG2.

Bursting properties of units in cat globus pallidus and entopeduncular nucleus: the effect of excitotoxic striatal lesions.

The bursting properties of units recorded in globus pallidus and entopeduncular nucleus were studied in awake cats sitting quietly before and after ipsilateral excitotoxic striatal lesions. A computerized statistical procedure was used to identify and evaluate bursts in the recorded spike trains. Bursts were assigned a quantitative statistical measure of burst 'strength' (or improbability) - the surprise value.

Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy.

We examined binding to excitatory amino acid and inhibitory amino acid receptors in frozen hippocampal sections prepared from surgical specimens resected from 8 individuals with medically refractory temporal lobe epilepsy. The excitatory receptors studied included N-methyl-D-aspartate (NMDA), strychnine-insensitive glycine, phencyclidine, and quisqualate. The inhibitory receptors studied were gamma-aminobutyric acid type A (GABAA) and benzodiazepine.

Interaction of Ca-channel blockers and high pressure at the crustacean neuromuscular junction.

Exposure to high pressure causes a significant depression of synaptic transmission. We examined the effects of various Ca-channel blockers and their interaction with high pressure on excitatory neuromuscular junction currents (EJCs) of lobster abdominal muscles. Reduced [Ca2+]o to half of normal concentration or exposure to 40-60 microM CdCl2, 10-20 microM NiCl2 and 1 microM omega-conotoxin decreased EJCs by 50%.

The temporal structure of spike trains in the primate basal ganglia: afferent regulation of bursting demonstrated with precentral cerebral cortical ablation.

We studied the temporal pattern of discharge of single units in the basal ganglia of awake primates sitting quietly. Bursting was studied with a procedure that identified individual bursts in a spike train, quantifying burst intensity (surprise), bursts per 1000 spikes, spikes per burst and burst length. Autocorrelation techniques were used to assess the dependencies of spike trains on the temporal order of intervals.

A 23187-stimulated calcium uptake and GABA release by cerebrocortical synaptosomes: effects of high pressure.

Guinea pig cerebrocortical synaptosome preparations were used to study the effect of compression to 62 ATA on 45Ca2+ uptake and [3H]GABA release using a calcium ionophore A 23187, which bypasses the voltage-sensitive calcium channel. Pressure was found to exert a suppressive effect on the A 23187-induced release of [3H]GABA, while having no significant effect on A 23187-stimulated 45Ca2+ uptake. On the other hand, both depolarization-induced 45Ca2+ uptake and [3H]GABA release were inhibited by pressure exposure.

Cerebellar and frontal hypometabolism in alcoholic cerebellar degeneration studied with positron emission tomography.

Local cerebral metabolic rate for glucose was studied utilizing 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 14 chronically alcohol-dependent patients and 8 normal control subjects of similar age and sex. Nine of the 14 patients (Group A) had clinical signs of alcoholic cerebellar degeneration, and the remaining 5 (Group B) did not have signs of alcoholic cerebellar degeneration. PET studies of Group A revealed significantly decreased local cerebral metabolic rates for glucose in the superior cerebellar vermis in comparison with the normal control subjects.

Cerebral glucose hypermetabolism in Friedreich's ataxia detected with positron emission tomography.

Local cerebral metabolic rate for glucose was studied with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 22 patients with Friedreich's ataxia and 23 age-matched normal control subjects. The diagnosis of Friedreich's ataxia was established by the history and physical findings and by excluding other diseases through laboratory investigations. PET studies revealed a statistically significant widespread increase of local cerebral metabolic rate for glucose in the brains of patients with Friedreich's ataxia who were still ambulatory, in comparison with normal control subjects.

Quisqualate- and NMDA-sensitive [3H]glutamate binding in primate brain.

Excitatory amino acids (EAA) such as glutamate and aspartate are probably the neurotransmitters of a majority of mammalian neurons. Only a few previous studies have been concerned with the distribution of the subtypes of EAA receptor binding in the primate brain. We examined NMDA- and quisqualate-sensitive [3H]glutamate binding using quantitative autoradiography in monkey brain (Macaca fascicularis).

The Marinesco-Sjögren syndrome examined by computed tomography, magnetic resonance, and 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography.

The Marinesco-Sjögren syndrome is an autosomal recessive degenerative disorder characterized by congenital cataracts, cerebellar ataxia, spasticity, mental deficiency, and skeletal abnormalities. We studied two adult siblings with Marinesco-Sjögren syndrome using anatomic and metabolic brain imaging techniques to characterize the pattern and nature of abnormalities in the brain. Computed tomographic and magnetic resonance imaging showed diffuse brain atrophy of mild to moderate degree, involving primarily the white matter of the cerebrum, cerebellum, brain stem, and cervical spinal cord.

Characterization of interleukin 1 induced rabbit chondrocyte phospholipase A2.

Stimulation of rabbit articular chondrocytes with interleukin 1 (IL-1) results in the activation of intracellular phospholipase A2 (PLA2) and the subsequent secretion of this enzyme into the extracellular milieu. Pretreatment of chondrocytes with actinomycin D or cycloheximide significantly inhibited IL-1 induced PLA2 activation and secretion, suggesting that the enzyme induction process is RNA and protein synthesis dependent. Chondrocyte PLA2 is highly calcium dependent with a 1 mM optimum CA++ concentration for hydrolytic activity; little or no hydrolysis is observed in the absence of calcium and the hydrolytic activity is abolished in the presence of 10 mM ethylenediamine tetraacetic acid.

Immunohistochemical and pharmacokinetic characterization of the site-specific immunoconjugate CYT-356 derived from antiprostate monoclonal antibody 7E11-C5.

In this study, a site-specific immunoconjugate, designated CYT-356, of the prostate-reactive monoclonal antibody 7E11-C5 was characterized by immunohistological methods for reactivity with normal and neoplastic human tissues. In addition, CYT-356 labeled with 111In was assessed by in vivo imaging and pharmacokinetic studies for localization to human tumor xenografts in nude mice. The native antibody and the site-specific immunoconjugate exhibited similar patterns of reactivity with normal human tissues.

Neuropsychological changes in olivopontocerebellar atrophy.

We used standardized neuropsychological measures of intellectual, cognitive, psychomotor, and emotional functioning to compare 39 patients with olivopontocerebellar atrophy and 25 normal controls of similar age. The patients reflected greater depression, anxiety, and subjective emotional discomfort than did the control subjects. While 4 of the patients had below-normal IQ scores (Wechsler Adult Intelligence Scale [WAIS-R] Full-Scale IQ [FSIQ] less than 80), their clinical histories suggested lifelong functioning at such levels.

Differences between lateral and mesial temporal metabolism interictally in epilepsy of mesial temporal origin.

We performed interictal [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in 17 patients with well-defined unilateral anterior mesial temporal epileptogenic foci as determined by EEG procedures. Sixteen of these patients subsequently underwent surgical resection of the epileptogenic focus. We measured local cerebral metabolic rates for glucose in mesial and lateral temporal structures and compared them with metabolic rates for analogous regions in 16 healthy normal volunteers and the contralateral hemisphere of the epileptic patients.

Two types of quisqualate receptors are decreased in human olivopontocerebellar atrophy cerebellar cortex.

We used receptor autoradiography to study the distribution of ionotropic and metabotropic quisqualate (QA) receptors in normal human cerebellar cortex and cerebellar cortex from 7 cases of olivopontocerebellar atrophy (OPCA). In normal human cerebellar cortex, both types of QA receptors were densest in the molecular layer. Both ionotropic and metabotropic QA receptors were significantly diminished in the molecular layer of OPCA specimens.

Autoradiographic localization of inhibitory and excitatory amino acid neurotransmitter receptors in human normal and olivopontocerebellar atrophy cerebellar cortex.

We used standard techniques of receptor autoradiography to study the distribution of inhibitory and excitatory amino acid neurotransmitter receptors in human normal cerebellar cortex. Benzodiazepine (BDZ) receptor density was relatively high in both granule cell and molecular layers. GABAA receptor density was highest in granule cell layer with lower receptor density in molecular layer.

Effect of helium and heliox on glutamate decarboxylase activity.

The activity of glutamate decarboxylase (GAD) in pure helium at 6.8 MPa was significantly enhanced when compared to GAD activity in air at 0.1 MPa (906 vs.

Spontaneous neuronal unit activity in the primate basal ganglia and the effects of precentral cerebral cortical ablations.

The discharge properties of single neuronal units in the putamen, caudate nucleus, and globus pallidus were studied in awake primates. The effects of restricted deafferentation of the striatum were determined by recording single unit activity in animals with unilateral ablation of areas 4 and 6 of Brodmann. The most striking change was on the regularity of unit firing in the putamen.

A multiwire microelectrode for single unit recording in deep brain structures.

A method is described by which a single shaft multiwire microelectrode can be fabricated efficiently. The resulting electrode can be attached to a commercial microdrive and used for single neuronal unit recording from one or more tracks in deep brain structures of anesthetized or awake animals. The electrode consists of a 30 gauge stainless steel cannula through which multiple strands of 13 micron insulated tungsten microwires are threaded.

Carbohydrate-derivatized immunoconjugate of the anti-(carcinoembryonic antigen) monoclonal antibody C46: immunohistological reactivity and pharmacokinetic comparison with a randomly derivatized C46 immunoconjugate.

In this study, a site-specific glycyl-tyrosyl-(N-epsilon-diethylenetriaminepentaacetic acid)-lysine (GYK-DTPA) immunoconjugate of the anti-carcinoembryonic antigen monoclonal antibody C46 (C46-GYK-DTPA) was characterized by immunohistological and immunofluorescence methods for reactivity with normal and neoplastic human tissues. In addition, pharmacokinetic studies assessed the ability of C46-GYK-DTPA labeled with 111In to localize to and image human tumor xenografts in nude mice. The native antibody and the site-specific immunoconjugate exhibited similar patterns of reactivity with normal human tissues.