Localization of neuroblastoma in vivo with tumor-specific antibodies.

Studies of the mouse C-1300 neuroblastoma were undertaken in order to isolate tumor-specific antibodies and harness them for detection of tumors in vivo. Preliminary investigations demonstrated the strain-growth specificity of the neuroblastoma in A/Jax male mice and established the requirement for tumor viability for successful adoptive passage. Intradermally passaged tumor permitted extended survival of mice so that serum could be sampled at intervals for the presence of tumor-specific antibodies. By means of an indirect radioimmunoassay with glutaraldehyde-fixed identified in the serum of tumor-bearing hosts 6 days after inoculation, with a steady increase in antibody levels observed through Day 22. An eluate in which immunoglobulin G antibodies were identified by immunoelectrophoresis was obtained from purified tumor cells by acid buffer incubation. These antibodies were labeled with 125-I, absorbed with normal tissues, and injected into tumor-bearing mice. A selectively collimated single-probe isotope localization was positioned over the intradermal tumor, while the rest of the animal was shielded with lead. With this device, 125-neuroblastoma eluate was significantly taken up in the neuroblastoma but not in the mouse head or in a reticulum cell sarcoma control. Increasing uptake of MOPC 141 125-I-immunoglobulin G was not observed in either tumor. These studies suggest that the mouse neuroblastoma may provide a source of tumor-specific, antibodies and that, with sensitive monitoring devices, these antibodies may be utilized to localize occult neoplastic tissue in vivo.

Augmentation of mortality risk discriminating power of left ventricular ejection fraction by measures of nonuniformity in systolic emptying on radionuclide ventriculography.

Employing equilibrium-gated radionuclide ventriculography in the left anterior oblique view, six geometric models and five mathematic coefficients of nonuniformity in regional left ventricular emptying were tested for their relative mortality risk-stratifying power and capacity to augment the risk-discriminating potency of the continuous and dichotomized global ejection fraction. Radionuclide ventriculography was performed an average of 7.6 days after acute myocardial infarction. All geometric models significantly separated 20 normal subjects from 137 patients with recent infarction (p less than 0.001). Cumulative mortality data demonstrated that significant independent univariate dichotomizing potency and augmentation of the mortality risk-discriminating power of the global ejection fraction were provided by models of regional emptying that 1) conformed to coronary artery perfusion areas, 2) encompassed total ventricular counts, 3) expressed variability in regional relative to global ejection fraction, and 4) simulated a pattern of emptying directed toward the center of geometry of the left ventricle. The combination of a four quadrant geometric model with axes drawn 45 degrees above the horizontal and a coefficient of variation calculated as square root of sigma(GEF - REF)2/4 x 100/GEF (where GEF = global ejection fraction and REF = regional ejection fraction) proved to be optimal. This coefficient averaged 12.2% in normal subjects and 32.2% in patients with recent acute myocardial infarction (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Search for cytomegalovirus in the postmortem brains of schizophrenic patients using the polymerase chain reaction.

Cytomegalovirus infection has a number of features that suggest a possible association between congenital infection and schizophrenia. Previous studies have investigated anticytomegalovirus antibody titers or attempted directly to identify viral antigens in body fluids or brain tissue from schizophrenic subjects but have been limited by the sensitivity of the available methods. The highly sensitive polymerase chain reaction, a newly developed technique for gene amplification, was used to search for cytomegalovirus in the DNA extracted from postmortem temporal cortex samples of eight schizophrenic subjects, eight nonschizophrenic suicide victims, and eight normal controls. Cytomegalovirus-specific DNA amplification was not detected in any of the samples. The implications of this finding for the viral hypothesis of schizophrenia are discussed.

Lack of evidence for a role of T-cell-associated retroviruses as an etiology of schizophrenia.

The evidence that schizophrenia may involve infection by a virus (or viruses) has been indirect. The recent discovery, however, of the human retroviruses--human T-cell lymphoma-leukemia virus-I, and II (HTLV-I, -II) and human immunodeficiency virus (HIV)--now also known to affect the central nervous system (CNS), together with the development of new techniques in retrovirology, have made it possible to investigate more directly the role of this class of viruses as an etiology of schizophrenia. In our first effort to screen for the presence of a T-cell lymphotropic virus in schizophrenia, short-term tissue cultures of peripheral lymphocytes from 17 chronic schizophrenic patients and 10 normal controls were established. The cells were cultured in the presence of T-cell growth factor (TCGF, IL-2), and the culture supernatants were tested for the presence of the retroviral enzyme reverse transcriptase. No T-cell-associated reverse transcriptase activity was detected in cultures from patients or normal controls. Therefore, the data do not provide evidence for a role for T-cell lymphotropic retroviruses as an etiology of schizophrenia.

Biological stability of mRNA isolated from human postmortem brain collections.

RNA isolated from frozen human postmortem brain tissue was evaluated for its utility in molecular biological studies. Samples varying in postmortem interval, delay period before freezing, and long-term freezer storage were analyzed. It was found that storage of human postmortem brain at -70 degrees C for more than 5 years may compromise its use for oligo-dT primed library construction and in vitro expression studies. Although biological competency of the messenger RNA may be affected by long-term freezer storage of human brain, enough full-length or partial transcripts remained for amplification by the polymerase chain reaction. We conclude that human postmortem brain collections will continue to be valuable resources for the study of gene expression and isolation of nucleotide sequences.

Defect symptoms and abnormal involuntary movement in schizophrenia.

Tardive dyskinesia (TD), a possible marker of the defect state of schizophrenia, was studied along with defect symptoms in 55 neuroleptic-treated chronic schizophrenic patients. Our cross-sectional data failed to replicate earlier findings of increased defect symptoms in TD patients (n = 14), except for more severe paucity of speech content when compared with non-TD patients (n = 41). Methodological issues that may account for some of the current and previously reported findings are discussed.

Abnormal cerebrospinal fluid protein indices in schizophrenia.

Determinations of albumin and immunoglobulin G (IgG) were performed in paired cerebrospinal fluid (CSF) and serum samples from 24 subjects with schizophrenia. These determinations allowed calculation of two indices, one that is an indicator of integrity of the blood-brain barrier and the other a measure of selective IgG production within the central nervous system (CNS). In comparison with previously determined reference values, 7 of 24 (29%) subjects showed increased blood-brain barrier permeability, and 8 of 24 (33%) demonstrated elevated endogenous CNS IgG production. One of these eight also demonstrated oligoclonal banding on high-resolution protein electrophoresis of the CSF.

Increased serum soluble interleukin-2 receptors in Caucasian and Korean schizophrenic patients.

Recent studies have identified immunologic abnormalities in some schizophrenic subjects. This experiment replicates previous findings that serum soluble interleukin-2 receptors (SIL-2Rs) are elevated in schizophrenic patients, and is the first study to describe this phenomenon in non-Caucasian patients. Despite differences between Korean and Caucasian schizophrenic patients in absolute serum SIL-2R levels, both groups were significantly elevated when compared with their respective ethnic control groups (477 +/- 171 U/ml versus 354 +/- 172 U/ml and 763 +/- 347 U/ml versus 567 +/- 231 U/ml, respectively). Neither age, gender, medication status, nor duration of illness correlated with SIL-2R levels. These findings are further evidence that immune activation is present, regardless of ethnic origin, in some schizophrenic patients.

Tardive dyskinesia: neuropsychological, computerized tomographic, and psychiatric symptom findings.

Prior studies have suggested that schizophrenic patients with tardive dyskinesia (TD) have an unusual incidence of cognitive impairment, structural brain abnormalities, and negative symptoms. Twenty-seven schizophrenic patients with TD and an equal number of age-, gender-, and education-matched schizophrenic controls were studied. Each patient received neuropsychological testing, psychiatric symptom ratings, and most had cerebral computed tomography (CT) scans. Patients with TD significantly differed from controls on only 1 of 23, cognitive measures, and the overall group performance profiles were highly similar. No differences were observed on symptom ratings. Patients with TD had significantly smaller ventricular-brain ratios (VBRs) than controls. These data fail to support an association of TD with global measures of "organicity." Abnormal movements may result from specific dysfunction within the more purely motor circuits of the basal ganglia without compromising other neural systems involved in cognitive processing.

Polydipsia and hyponatremia in psychiatric patients.

Many psychiatric patients have polydipsia and polyuria without identifiable underlying medical causes. Hyponatremia develops in some polydipsic patients and can progress to water intoxication with such symptoms as confusion, lethargy, psychosis, and seizures or death. This syndrome is sometimes called "compulsive water drinking," "psychogenic polydipsia," and "self-induced water intoxication." Although the underlying pathophysiology of the syndrome is unclear, several factors have been implicated in producing polydipsia and symptomatic hyponatremia. These include a possible hypothalamic defect, the syndrome of inappropriate secretion of ADH (SIADH), and neuroleptic medication. Evaluation of psychiatric patients with polydipsia includes a search for other medical causes of polydipsia, polyuria, hyponatremia, and SIADH. Treatment modalities currently available include fluid restriction and medications.

Treatment of schizophrenia with a vasopressin analogue.

Ten patients with chronic schizophrenia completed a 3-month double-blind, placebo-controlled trial with a vasopressin analogue. Modest improvement occurred, but several patients also experienced significant fluid and electrolyte imbalance.

MRI changes during water loading in patients with polydipsia and intermittent hyponatremia.

OBJECTIVE: Patients with polydipsia and intermittent hyponatremia have greater ventricle-brain ratios (VBRs) than matched patients without polydipsia and intermittent hyponatremia and normal subjects. Unlike previous studies, this study controlled for the impact of water loading when examining the volume of intracranial structures. METHOD: Under controlled conditions, eight male schizophrenic patients with polydipsia and intermittent hyponatremia were first assigned to either normal fluid intake or oral water loading and then the alternative condition the following day. Magnetic resonance imaging (MRI) volumetric measurements were made with the use of a standardized protocol. RESULTS: During water loading, total VBR and lateral ventricle volume significantly decreased by 13.1% and 12.6%, respectively. A strong association between change in serum sodium concentration and change in VBR was noted across conditions. CONCLUSIONS: These findings indicate that 1) water loading does not account for the diminished brain volume observed in patients with polydipsia and intermittent hyponatremia in previous studies, and 2) hyponatremia can significantly alter brain morphology on MRI.

Sustained release nitroglycerin improves myocardial thallium-201 images in men with coronary artery disease.

Ten men with coronary disease and angina-limited exercise participated in a study of the effects of sustained release nitroglycerin capsules on exercise performance and myocardial thallium images. Dose titration to ascertain the maximally tolerated dose, 6.5 to 26 mg orally four times a day, followed by double-blind, placebo-controlled cross-over treatment was undertaken. Following the administration of sustained release nitroglycerin exercise performance and exercise thallium images improved and appeared to remain so for four hours.

Electrophysiological interactions between haloperidol and reduced haloperidol, and dopamine, norepinephrine and phencyclidine in rat brain.

Haloperidol and its metabolite, reduced haloperidol, were compared as antagonists of catecholaminergic neurotransmission in central nervous system of the rat. Agonists and antagonists were applied from multibarrelled micropipettes, which were also used to record extracellularly the effects of these substances on neuronal discharge. Haloperidol antagonized dopaminergic inhibition of caudate neurons and inhibition of cerebellar Purkinje neurons induced by noradrenaline, whereas reduced haloperidol was an ineffective antagonist. Phencyclidine, which is an indirect dopaminergic agonist in the caudate, caused inhibition of the discharges of caudate neurons resembling that induced by dopamine itself. These indirect effects of phencyclidine were also antagonized by haloperidol but not by reduced haloperidol. The data suggest that the metabolite, reduced haloperidol, is not an effective neuroleptic drug in the central nervous system.

Effect of chronic caffeine administration on monoamine and monoamine metabolite concentrations in rat brain.

Caffeine was chronically administered in four doses (0, 10, 25, and 50 mg/kg/day) to rats via twice-daily intraperitoneal injections for 30 days. Concentrations of brain tissue monoamines, dopamine (DA), norepinephrine (NE), and serotonin (5HT), and monoamine metabolites, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5HIAA), were determined. At the 10 mg/kg/day dose, no significant changes were found compared with controls. At 25 mg/kg/day and 50 mg/kg/day significant changes were observed within each monoamine system. In striatum, DA and 5HT were increased, while DOPAC was decreased. In frontal cortex, NE was increased. In cerebellum, 5HT and MHPG were increased.

Rapid, rigorous computation of modulation transfer function on a pocket calculator.

This article describes a method for the rigorous calculation of modulation transfer function (MTF) of a collimated scintillation detector using a programmable pocket calculator. The calculation utilizes a normalized discrete Fourier transform (DFT) of the line spread function (LSF) including real and imaginary terms. A method is described for recording the LSF using an Anger camera and multichannel analyzer (MCA). The procedures for recording of the LSF and calculation of the MTF are therefore performed independently of a computer, allowing nuclear medicine laboratories without access to a computer, allowing nuclear medicine laboratories without access to incorporate MTF studies into their quality-assurance programs. The results obtained using the pocket calculator were compared with those using a PDP-12 minicomputer. The pocket calculator was slightly more accurate, since it does not suffer from the round-off errors of the PDP-12. The time required to plot an 11-point MTF curve using the pocket calculator was 5 min, using the PDP-12 0.5 min.

A new method of multiplanar emission tomography using a seven pinhole collimator and an Anger scintillation camera.

A new method of multiplanar emission tomography is described; it uses a wide-field Anger scintillation camera (37.5 cm crystal diameter) and a seven-pinhole collimator. The pinholes (5.5 mm) acquire data simultaneously from the emissing source and project the data onto seven independent regions of the camera crystal. Multiple planes are reconstructed from the initial seven-view data acquisition through the use of a computerized addition-multiplication algorithm and variation of the superposition relationships among the projected views. These planes are then altered iteratively by a least-error criterion following ray-sum comparison with the original views. Planar resolution (full-width-half-maximum) is 1.0 cm and depth resolution is 1.5 cm. In 42 patients with angiographically demonstrated coronary-artery disease, studies of myocardial Tl-201 perfusion, under exercise, have shown improved detection sensitivity in comparison with scintigraphy using parallel-hole collimation.

Single-photon emission tomography with a 12-pinhole collimator.

To assess the advantages of more complete angular sampling and of more views in the tomographic reconstruction process, tomographic imaging with a 12-pinhole (12PH) collimator has been compared with 7-pinhole tomography (7PH). The 12PH system gives a 50% increase in sensitivity but resolution degrades more rapidly with depth. The 7PH and 12PH systems provide similar accuracy of detection of lesions in a myocardial ring phantom. The 7PH images, however, demonstrated more noise and "ripple" artifacts. The 12PH system offers a larger reconstruction volume and generates fewer artifacts when the collimator is misaligned with the myocardial long-axis, thus making patient positioning less critical than with 7PH. A disadvantage is that individual views are minified by the 12PH collimator, and a 256 X 256 image matrix should be used during image acquisition to limit digital sampling errors.

Seven-pinhole tomography--a technical description.

A single-photon emission tomography system was developed and studied. Based upon a seven-pinhile-collimated Anger camera, interfaced to a digital minicomputer, this imaging configuration yielded seven independent, nonoverlapping projection images of the radioactivity in a commonly viewed volume. The computer was used to implement an iterative algorithm that processed these projections to yield a three-dimensional reconstruction of the soruce distribution. The algorithm provudes a nonlinear first approximation to the reconstruction, then use a single iteration technique to reduce errors resulting from that approximation. Point spread functions (PSF) at various distances from the collimator face, and point-source sensitivity (PSS) at a location in the middle of the reconstruction volume were determined. The system was used for thallium-201 imaging, where it was shown to reduce imaging time and increase sensitivity without loss in specificity when compared with standard parallel-hole-collimated imaging. Seven-pinhole tomography is a practical three-dimensional imaging system that has been demonstrated to be useful in the emission cardiology setting.

Quality control of scintillation cameras using a minicomputer.

A minicomputer-based technique compiles objective indicators of scintigraphic system performance. The evaluation begins with the acquisition of a single image of an orthogonal hole pattern from which quantitative and regional measurements of point-source sensitivity, spatial resolution, and spatial linearity are derived. Two computer programs offer the user different but complementary features. The first program is the basis of an evaluation performed by a technologist for purposes of quality control. Operator intervention is minimal, and the entire protocol, including data acquisition and processing, can be completed in 20 min. The results are automatically compiled and displayed as graphs showing 100 consecutive sets of daily performance measurements. A second computer program is designed as an interactive diagnostic and research tool to display measurements as histograms and functional images. The operator can use the program to determine the quantitative and spatial characteristics of the system's intrinsic performance measurements made during the quality-control evaluations.