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Biomedical subjects

G Bruder

Publications and source records attributed to G Bruder.

At least 19 recordsLinked to original sources

Schizophrenia subgroups differing in dichotic listening laterality also differ in neurometabolism and symptomatology.

Schizophrenia patients vary in right ear advantage (REA) on dichotic listening tests for assessing left hemispheric dominance for language processing. The authors examined if patients with low REA differed from other patients in symptoms and in resting brain metabolism. SPECT was conducted during visual fixation for 9 healthy control subjects and 16 schizophrenia patients: 8 with normal and 8 with diminished REA. REA-diminished patients had greater positive symptoms and lower mental status scores (all P<0.05) and had right middle temporal gyrus hypermetabolism. Both schizophrenia groups had decreased right frontal and increased medial temporal lobe metabolism vs. control subjects. REA-diminished patients had right temporal lobe hypermetabolism under a resting condition (eyes open, visual fixation). Results suggest reduced right ear (left hemisphere) advantage for dichotic word perception in schizophrenia is related to a predisposition to overactivate right temporal lobe regions and to positive symptoms. In contrast, the prefrontal-medial temporal imbalance present in both patient groups may typify the schizophrenia syndrome.

Adult↗

Left temporal lobe dysfunction in schizophrenia: event-related potential and behavioral evidence from phonetic and tonal dichotic listening tasks.

BACKGROUND: Asymmetric reduction of the P3 event-related potential (ERP) has provided evidence of left temporal lobe dysfunction in schizophrenia. Prior studies have been limited by reliance on simple target detection (oddball) tasks with pure tones. This study investigated the time course and topography of ERPs to binaural syllables or complex tones in dichotic listening tasks. METHODS: Event-related potentials of 26 patients meeting criteria for schizophrenia (n = 19) or schizoaffective disorder (n = 7) and 26 healthy controls were recorded from 30 scalp electrodes during 2 dichotic tasks in which different syllables or complex tones were simultaneously presented to each ear. A principal components analysis was used to derive factor scores corresponding to overlapping components in ERP waveforms--N1, N2, P3, and a late-positive potential. RESULTS: Healthy controls showed a right ear advantage for perceiving dichotic syllables, which was associated with greater N2 amplitude at left than right temporoparietal sites. Patients with schizophrenia did not show either this perceptual or N2 asymmetry. Patients also had smaller late-positive potential amplitude when compared with controls for both syllables and complex tones, with greatest decrement over left temporal sites. CONCLUSIONS: A right ear advantage in healthy adults for perceiving consonant-vowels was associated with a left-lateralized ERP component peaking at 200 milliseconds after syllable onset (N2). Patients with schizophrenia failed to show either of these task-dependent asymmetries, which may indicate a dysfunction of left temporal regions involved in phonetic classification. A task-independent asymmetric reduction of a later positive potential in patients with schizophrenia resembled left temporal P3 reductions reported for auditory oddball tasks.

Acoustic Stimulation↗

Psychobiological heterogeneity of familial and sporadic schizophrenia.

BACKGROUND: Although schizophrenia is presumed to be heterogeneous, there has been limited success distinguishing familial from sporadic cases. We used psychobiological measures to examine heterogeneity, as they may be closer to neurobiology than symptoms. Smooth pursuit eye movement quality (SPEM) and dichotic listening (DL) tests to tones and words were used to assess hemispheric laterality asymmetry. METHODS: Forty-six research unit patients participated in assessments of family history (FH) and physiological measures. FH was categorized by three exclusive groups: FH-1 patients had a chronic schizophrenia-related psychosis in a first-degree relative, FH-2 had it in second-degree relative, and FH-3 had no family member with a reoccurrence. RESULTS: Analysis of variance showed a significant group difference for SPEM and DL tones. SPEM was significantly worse in all three schizophrenia groups than for the normal comparison subjects. Among the schizophrenia groups, the nonfamilial group (FH-3) had the worst SPEM quality, FH-2 had intermediate quality, and FH-1 had the best quality. Conversely, only the nonfamilials (FH-3) had normal right hemispheric lateralization for tones, whereas familials did not, and FH-2 again had intermediate values. The lateralization quotient for DL words did not significantly differ among the groups. CONCLUSIONS: SPEM was affected most in sporadic, not familial schizophrenia, whereas dichotic listening was most affected in familial schizophrenia. This double dissociation supports the utility of the familial/sporadic distinction and suggests that etiological factors in different forms of schizophrenia may impact principally on distinct neurobiological substrates, despite similar patient phenomenology.

Adult↗

The time course of visuospatial processing deficits in schizophrenia: an event-related brain potential study.

Event-related brain potentials (ERPs) were recorded during a dot enumeration task so as to investigate electrophysiologic correlates of early visuospatial processing in schizophrenia. Twenty-eight patients having a diagnosis of schizophrenia (n = 19) or schizoaffective disorder (n = 9) and 28 controls were tested. Patients showed poorer dot enumeration than did controls and also had markedly reduced early negative ERPs, which began about 150 ms after stimulus onset at the peak of the N1 potential and reached its maximum about 275 ms at the N2 peak. The N1 reduction in patients was greatest over left parietal sites for stimuli in the right visual field. The marked N1 and N2 reductions in patients are supportive of models postulating deficits in early visuospatial attention and allocation of conceptual resources in schizophrenia.

Adult↗

Diminished cardiac vagal tone in schizophrenia: associations to brain laterality and age of onset.

We measured high-frequency (rapid) heart rate variability (HRV) from 24-hour Holter electrocardiograms to index cardiovagal tone in 23 patients with DSM-III-R schizophrenia or schizoaffective disorder. High-frequency HRV, quantitated by measuring the percent of successive normal interbeat intervals greater than 50 msec (PNN50), demonstrated a bimodal distribution: 11 of 23 patients had a PNN50 of > and = 8.0 (mean value = 17.7 +/- 11.0), and 12 had a PNN50 of < and = 4.0 (mean value = 1.8 +/- 1.0); no subject had a PNN50 value between 4.0 and 8.0. All 12 low cardiovagal tone patients (versus only 6/11 of the other patients) had a schizophrenia (not schizoaffective) diagnosis (p = .013). PNN50 was not associated with present age, gender, smoking, IQ scores, or symptomatology, but patients with lower cardiovagal tone did have a significantly later age of onset (20.5 +/- 5.3 vs. 14.8 +/- 2.8 years: p = .005). PNN50 subgroups also differed on dichotic listening measures of brain laterality. The low group failed to show left ear (right hemisphere) advantage for complex tones seen in the other patients and normal adults. They also showed larger right ear (left hemisphere) advantage for dichotic words than the other patients. This evidence of relative right hemisphere disadvantage in patients with low cardiovagal tone is consistent with findings linking autonomic nervous system and right hemisphere function. These findings also support the existence of subgroups of schizophrenia patients differing in autonomic activity, brain laterality, and clinical features.

Adult↗

Abnormality of EEG alpha asymmetry in female adolescent suicide attempters.

Abnormal electroencephalographic (EEG) activity has been associated with various psychiatric disorders and behaviors, including depression, suicide, and aggression. We examined quantitative resting EEG in Hispanic female adolescent suicide attempters and matched normal controls. Computerized EEG measures were recorded at 11 scalp sites during eyes open and eyes closed periods from 16 suicide attempters and 22 normal controls. Suicide attempters differed from normal controls in alpha asymmetry. Normal adolescents had greater alpha (less activation) over right than left hemisphere, whereas suicidal adolescents had a nonsignificant asymmetry in the opposite direction. Nondepressed attempters were distinguished from depressed attempters in that they accounted for the preponderance of abnormal asymmetry, particularly in posterior regions. Alpha asymmetry over posterior regions was related to ratings of suicidal intent, but not depression severity. The alpha asymmetry in suicidal adolescents resembled that seen for depressed adults in its abnormal direction, but not in its regional distribution. Findings for suicidal adolescents are discussed in terms of a hypothesis of reduced left posterior activation, which is not related to depression but to suicidal or aggressive behavior.

Adolescent↗

Smaller right ear (left hemisphere) advantage for dichotic fused words in patients with schizophrenia.

OBJECTIVE: The purposes of this study were to compare right ear (left hemisphere) advantage for dichotic words in schizophrenia and depression and to assess its association with antipsychotic medication, symptom ratings, and gender. METHOD: Thirty-two schizophrenic patients and 65 patients with major depression were given the Fused Rhymed Words Test, a dichotic listening measure of hemispheric dominance for language. RESULTS: An earlier finding of smaller left hemisphere advantage in schizophrenic patients was replicated. There was no significant change in ear advantage in a subgroup of the schizophrenic patients tested when they were taking neuroleptics and when they were not. The smaller left hemisphere advantage in the schizophrenic patients was not dependent on gender but was related to symptom ratings on the Positive and Negative Syndrome Scale. CONCLUSIONS: The findings are consistent with a left hemisphere dysfunction in schizophrenia, which is associated with positive symptoms.

Adult↗

Event-related potential and clinical correlates of neurodysfunction in obsessive-compulsive disorder.

The current study confirmed with increased sample sizes our preliminary findings of event-related potential (ERP) abnormalities in obsessive-compulsive disorder (OCD) (Towey et al., 1990) and examined their relationship to symptom severity, treatment response, and neurological soft signs. Unmedicated patients (n = 17) showed larger negativities in N200 and slow wave regions than normal control subjects (n = 16) to correctly detected auditory "oddball" stimuli. N200 amplitude was larger over left than right hemispheres of OCD patients, but not normal control subjects. Greater N200 amplitude correlated with less severe obsessions, better response to subsequent treatment with serotonin reuptake blockers, and fewer neurological soft signs in OCD. With increased task difficulty, N200 and P300 latencies lengthened for normal subjects, but not for OCD patients. The abnormal ERP pattern in OCD supports hypotheses of cortical hyperarousal and overfocused attention.

Adult↗

Endogenous event-related potentials in obsessive-compulsive disorder.

Brain event-related potentials (ERPs) were used to investigate central nervous system (CNS) correlates of cognitive function in obsessive-compulsive disorder (OCD). ERPs of 10 unmedicated OCD patients and 10 normal controls were measured in an auditory "oddball" task. Increasing task difficulty resulted in longer N200 and P300 latencies in normal subjects, but not in OCD patients. Moreover, OCD patients displayed shorter P300 latency than normal controls for the more difficult discrimination conditions. This replicates prior findings of Beech et al. (1983) for a visual task. For both levels of task difficulty, OCD patients also showed greater negativity than normal controls in the N200 region, which extended into the subsequent slow wave region. Negativities in the N200 and slow wave regions were larger at sites over the left hemisphere than the right hemisphere. The enhanced negativities and reduced P300 latency in OCD patients are discussed in terms of current theories postulating cortical hyperarousal and left hemisphere involvement in OCD.

Adolescent↗

Localization of xanthine oxidase in crystalline cores of peroxisomes. A cytochemical and biochemical study.

The ultrastructural cytochemical localization of xanthine oxidase activity in rat liver was investigated by the cerium technique. The reaction product was found in the cytoplasm of endothelial cells in liver sinusoids and, in addition, in crystalline cores of peroxisomes of liver parenchymal cells. Xanthine oxidase was also present in peroxisomal cores of beef liver and kidney, but not in rat kidney peroxisomes, which lack crystalline cores. The localization in peroxisomal cores of rat liver was confirmed also biochemically using highly purified peroxisomal fractions and subfractions containing exclusively the crystalline cores. Moreover, high levels of molybdenum were found in isolated peroxisomal cores by atomic absorption spectroscopy, thus corroborating the association of the molybdenum-containing enzyme with the cores. Since urate oxidase is also present within the same compartment of peroxisomes, it is possible that the crystalline cores harbor a complex of several enzymes involved in the purine metabolism.

Animals↗

Identification of a distinct 9S form of soluble clathrin in cultured cells and tissues.

We have used a monoclonal antibody (CHC5.9) to identify clathrin (Mr 180,000; 'heavy chain') in coated vesicles, triskelion structures prepared in vitro and in high-speed supernatants (HSS) of cell homogenates from a variety of tissues and species (e.g., brain and liver from rat, cow and man; Xenopus ovaries). HSS proteins were subjected to sucrose density gradient centrifugation and gel filtration, and the fractions obtained were assayed for clathrin by enzyme-linked immunosorbent assay (ELISA) and polyacrylamide gel electrophoresis (PAGE), followed by immunoblotting. The native soluble clathrin identified in such fractions was indistinguishable from triskelions produced in vitro from purified bovine brain clathrin by several criteria, e.g. by its sedimentation coefficient (9S) and elution profile on gel filtration using Sephacryl S 300. No other major forms of soluble clathrin were detected. The results indicate that cells contain a soluble pool of clathrin and that the predominant molecular form of this soluble clathrin has properties similar to those of the triskelion obtained by dissociation studies in vitro. We hypothesize that this distinct 9S form represents a major oligomeric subunit involved in assembly and disassembly of clathrin polyhedron coats in the living cell.

Animals↗

Significance of xanthine oxidase in capillary endothelial cells.

Antibodies to xanthine oxidase from bovine milk lipid globules localize the antigen in capillary endothelial cells of many tissues including liver, heart, lung and kidney, but not in other epithelial, endothelial or mesenchymal cell types. The antigen from bovine capillaries was purified by immunoaffinity chromatography and shown by chemical, enzymatic and immunological methods to be indistinguishable from milk xanthine oxidase. Using an ultrasensitive radioimmunoassay, concentrations of this protein were found to be 1 000-10 000-fold higher in capillary endothelial cells than in other cells studied except mammary epithelial cells which were also rich in xanthine oxidase. Similar results were obtained with human cells and tissues. In the cytoplasm of capillary endothelial cells, xanthine oxidase was present as a dehydrogenase which was rapidly converted to the O-2-radical-producing oxidase form after release by cell disrupture. This conversion was partly prevented by addition of thiol reagents. Free xanthine oxidase was not detected in human serum, even from patients with extensive capillary lesions. However, specific-apparently constitutive--antibodies (IgG) were present at high concentrations (1-8% of total IgG) in the sera of all individuals tested. A role of these specific antibodies in the removal of the potentially hazardous oxidase form of xanthine oxidase is discussed.

Adenocarcinoma↗

Characterization of a monoclonal antibody to bovine xanthine oxidase.

The isolation of a hybridoma cell line, C-41, secreting monoclonal antibody to bovine xanthine oxidase (EC 1.2.3.2), is described. The specificity of this antibody was determined by solid-phase immunoassay, immunoblotting procedures, affinity chromatography, immunoelectrophoresis and precipitation techniques. The results are compared with those obtained in similar specificity studies on a previously described monoclonal antibody secreted by hybridoma cell line A-94 [Mather, Nace, Johnson & Goldsby (1980) Biochem. J. 188, 925-928]. This latter antibody appears to bind to xanthine oxidase only when the enzyme is immobilized on a solid support such as a plastic plate or nitrocellulose paper. Potential problems in the determination of the specificity of monoclonal antibodies, especially towards membrane proteins of unknown biological activity, are discussed.

Animals↗

Protein synthesis in lactating guinea-pig mammary tissue perfused in vitro. I. Radiolabelling of membrane and secretory proteins.

A method for the in vitro perfusion of isolated guinea-pig mammary tissue is described that allows the radiolabelling of secretory and membrane proteins. Glands were depleted of methionine, labelled with [35S]methionine for 5 min and perfused with medium containing an excess of unlabelled methionine for varying times. The structural integrity of the alveoli in the perfused glands appeared well maintained. Epithelial polarity was preserved and junctional complexes were evident. About 20% of the methionine provided in the medium was extracted by glands of 10 g wet weight under the labelling conditions employed. With chase periods from 15 to 40 min, 50-70% of the methionine was incorporated into trichloroacetic-acid (TCA)-precipitable material. The principal radiolabelled proteins recovered from the tissue fractions had Mrs and isoelectric points similar to the major secretory proteins (i.e. caseins and alpha-lactalbumin) of guinea-pig milk. Autoradiography of tissue sections at the resolution of the light microscope showed that secretory proteins were transported from sites of synthesis within secretory cells to the alveolar lumina after 45 min. These highly labelled secretory proteins could be almost completely removed from microsomal fractions by treatment with sodium carbonate solutions. Proteins with Mrs from 30 000 to 200 000 were detected in the washed membranes by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and fluorography. These labelled membrane-associated proteins persisted in the microsomal membrane fraction after chase periods from 7.5 to 40 min.

Animals↗

Protein synthesis in lactating guinea-pig mammary tissue perfused in vitro. II. Biogenesis of milk-fat-globule membrane proteins.

Guinea-pig mammary tissue was perfused in vitro, radiolabelled with [35S]methionine and intracellular protein precursors of the milk-fat-globule membrane (FGM) recovered by immunoabsorption techniques. Labelled xanthine oxidase was solely detected in post-microsomal supernatants and butyrophilin in carbonate-washed membranes. A major glycoprotein (Gp 55), was initially present in a membrane-bound form, but after longer perfusion times a fraction of this protein was recovered in the post-microsomal supernatant. These results are discussed with reference to formation of the apically-derived FGM.

Animals↗

High concentrations of antibodies to xanthine oxidase in human and animal sera. Molecular characterization.

The widespread occurrence of antibodies (IgG) specific to xanthine oxidase in both normal (nonimmune) human and animal sera, and in antisera raised against a diversity of unrelated antigens is described. A study of sera from 81 humans revealed that xanthine oxidase-specific IgG represents a high proportion (1-8%) of total IgG. No obvious correlation to pathological events or symptoms of disease could be found. These xanthine oxidase-specific antibodies could be isolated by immunoaffinity chromatography on purified human or bovine xanthine oxidase and showed specific binding to the enzyme polypeptide of Mr 155,000 in immunoblotting experiments. By immunofluorescence microscopy they displayed the same cell type-specific reaction as experimentally induced antibodies, i.e., the staining of lactating mammary gland epithelium and capillary endothelium. The naturally occurring xanthine oxidase-specific antibodies consisted of polyclonal IgG of various subclasses. F(ab')2 preparations gave immune-reactions identical to those of IgG. The human xanthine oxidase-specific IgG cross-reacted with the bovine enzyme and both human and animal antibodies partially inhibited its activity. The xanthine oxidase activity of human milk lipid globules and supernatant fractions from various human tissues was extremely low when compared with that of the bovine antigen. The enzyme protein, however, was effectively precipitated from these sources by both the human and bovine antibodies. We suggest that the exceptionally high concentrations of antibodies against one protein, xanthine oxidase, are due to self-immunization to the xanthine oxidase antigen present in endothelial cells of capillaries. We do not exclude, however, nutritional contributions of bovine milk antigen to the appearance of xanthine oxidase antibodies in human sera. The possible biological functions of this immunological reaction are discussed.

Animals↗

Butyrophilin, an apical plasma membrane-associated glycoprotein characteristic of lactating mammary glands of diverse species.

Lipid globule membranes were isolated from human and bovine milk and from the milk of sheep, goat, pig, rat and guinea pig, and their polypeptide compositions were analyzed. The major polypeptides with molecular weights similar to that of bovine butyrophilin were separated by gel electrophoresis, isolated and characterized with respect to isoelectric point, molecular weight, immunological cross-reactivity and peptide composition after proteolytic cleavage. We show that in all species examined these proteins are similar to bovine butyrophilin in (i) their relative insolubility in buffers of low and high ionic strength and in non-denaturing detergents, (ii) the occurrence of several isoelectric variants, and (iii) patterns of peptides obtained by protease digestion. It is concluded that closely related proteins are major constituents of the cytoplasmic coat structures associated with milk lipid globule membranes of many species, and we propose the name butyrophilins for this group of proteins. Bovine and human butyrophilins are glycosylated with relatively large amounts of glucosamine, mannose, glucose and galactose but little fucose, sialic acids or galactosamine. Most if not all of the sugar residues are associated with an acetone-soluble peptide fragment of Mr 12000-16000 focusing at about pH 4.0. We suggest that this fragment contains a membrane-spanning peptide sequence and is involved in the attachment of the cytoplasmic coat to the membrane of the milk lipid globule.

Animals↗