The brain/mind complex. An epistemological approach.

It is stressed that the brain/mind complex constitutes a monolithic system that functions with emergent properties at several levels of hierarchical organization. These hierarchical levels are non-reducible to one another; they are at least three (neuronal, functional, and semantic), and they function within an interactional plan. From the epistemological view-point, the brain/mind complex uses logical and non-logical mechanisms to deal with day-to-day problems. Logic is necessary for the thinking process, but it is not sufficient. Emphasis is given to non-logical mechanisms; fuzzy logic and heuristics, which allow the mind to develop strategies to find solutions, are analysed.     

Extracellular characteristics of putative cholinergic neurons in the rat laterodorsal tegmental nucleus

The extracellular electrophysiological properties of neurons in the laterodorsal tegmental nucleus (LDT), a major source of cholinergic afferents to the thalamus, were studied in chloral hydrate-anesthetized rats. A combination of antidromic activation from the thalamus and histological verification of recording sites was used to correlate the identity of extracellular recordings in the rat LDT with cholinergic neurons in that region. All neurons antidromically activated by stimulation of the anteroventral thalamus were histologically verified to be within clusters of cholinergic (NADPH-d-positive) cells in the LDT or in the adjacent nucleus locus coeruleus (LC). The thalamically projecting LDT neurons had a homogeneous neurophysiological profile consisting of long duration action potentials (mean = 2.5 ms), slow conduction velocities (mean = 0.78 m/s), and lengthy chronaxie values (mean = 0.725 ms). The appearance and axonal characteristics of these neurons resembled those of noradrenergic LC neurons, but the two populations exhibited substantially different spontaneous activity patterns and sensory responsiveness. These characteristics may be useful in the preliminary identification of putative cholinergic neurons in vivo, and thereby provide a foundation for exploring the neuropharmacology, afferent modulation, sensory responsiveness and behavioral correlates of the brainstem cholinergic system.     

Diabetes mellitus. II: Routine chest radiography.

Chest radiographs of 43 consecutive diabetic patients were evaluated with a view to determine their role as a routine investigation of patients with diabetes mellitus. 22 (51.2%) patients had normal chest radiographs. The remaining 21 patients had 61 abnormalities found in their chest radiographs. 26 (42.6%) of these were significant abnormalities while 35 (57.4%) were non-significant. Of the former, 42.3% were due to cardiomegaly while in the latter group, aortic unfolding was the main finding. Radiological abnormalities were more commonly observed in patients aged 40 years and over, than in those below, with a ratio of 3:1. Chest radiographs corroborated clinical diagnosis in 19 of the 21 cases in whom abnormalities were observed. This study shows that routine chest radiograph in diabetic patients is useful in those with clinical symptoms and in older diabetics above the age of 40 years.     

The precision of positron emission tomography: theory and measurement

The limits of quantitation with positron emission tomography (PET) are examined with respect to the noise propagation resulting from radioactive decay and other sources of random error. Theoretical methods for evaluating the statistical error have been devised but seldom applied to experimental data obtained on human subjects. This paper extends the analysis in several ways: (1) A Monte Carlo method is described for tracking the propagation of statistical error through the analysis of in vivo measurements; (2) Experimental data, obtained in phantoms, validating the Monte Carlo method and other methods are presented; (3) A difference in activation paradigm, performed on regional CBF (rCBF) data from five human subjects, was analyzed on 1.6-cm diameter regions of interest to determine the mean fractional statistical error in PET tissue concentration and in rCBF before and after stereotactic transformation; and (4) A linear statistical model and calculations of the various statistical errors were used to estimate the magnitude of the subject-specific fluctuations under various conditions. In this specific example, the root mean squared (RMS) noise in flow measurements was about three times higher than the RMS noise in the concentration measurements. In addition, the total random error was almost equally partitioned between statistical error and random fluctuations due to all other sources.     

Humoral and cellular immunity following severe head injury: review and current investigations.

Infection is a common and serious complication of severe head injury. Immunocompetence in 25 severely head injured patients was investigated by measuring: (1) delayed-type hypersensitivity (DTH) skin test responses to common antigens; (2) phytohaemagglutinin (PHA) stimulated peripheral blood lymphocyte (PBL): blastogenesis, phenotype expression, and lymphokine production; (3) lymphokine-activated killer (LAK) cytotoxicity, antibody dependent cellular cytotoxicity (ADCC) and natural killer (NK) cytotoxicity; and (4) immunoglobulin and complement levels. The incidence of anergy to DTH skin testing was 100%. There was a decrease in PHA stimulated: PBL blastogenesis (p = 0.002), T-cell expression (p = 0.018), helper T-cell expression (p less than 0.001), interleukin-2 receptor expression (p less than 0.001), interleukin-2 production (p = 0.035) and gamma-interferon production (p less than 0.001). LAK cytotoxicity was depressed following incubation with IL-2 (p less than 0.001). There was no significant decrease in immunoglobulin levels and all acute phase reactants tested increased. The results of this study indicate that the cellular arm of immune response, including lymphocyte activation and cytokine production, is suppressed following severe head injury. The lack of enhancement in LAK cytotoxicity following incubation of PBLs with interleukin-2 suggests that factors other than decreased interleukin-2 production, such as the inherent lymphocyte dysfunction, other soluble mediators or suppressor cells, may be responsible for the reduction in cellular immunity observed following severe head injury.     

Multiple sclerosis in Galion, Ohio: prevalence and results of a case-control study.

An investigation of the occurrence of multiple sclerosis (MS) was undertaken in the City of Galion, Ohio, USA, because of a report of an increased number of cases. As of June 1, 1987, there were 18 living cases of MS in Galion and Polk Township, for a prevalence rate of 112 cases per 100,000 population. The expected rate is approximately 65-170 cases per 100,000. In a case-control study, residents of Galion or Polk Township who had MS were compared to residents who did not have MS. The controls were matched to the cases on age and sex and had lived in Galion for at least as long as their matched case. The cases and controls did not differ in the distribution of their present or past Galion addresses, occupational histories or workplace exposures. Cases were more likely to have graduated from high school and college than controls. Cases were more likely than controls to report a history of allergies, to recall two or more relatives who had neurologic diseases that began before their first MS symptoms, to report owning a cat that died of unexplained causes and to recall having received oral polio vaccine. Cases and controls had similar levels of antibodies to measles, chickenpox, cytomegalovirus and the human T-cell lymphotrophic virus I.     

Early computed tomographic scanning after resection of brain tumors in children

Enhanced and non-enhanced computed tomography (CT) brain scans were performed within 72 h of surgery on 21 children in whom brain tumors had been resected totally or subtotally, and scans were repeated at varying intervals thereafter. Biopsies of the resection margins were performed in 12 patients at the end of the surgical procedure. The immediate CT scan showed enhancement in the resection margin in 13 of the 21 patients and in 9 of the 13, the enhancement disappeared on follow-up scans. There was discordance between the results of immediate CT scan examination and the biopsies of the resection margins in 7 of the 12 cases. The advantages and disadvantages of an immediate postoperative scan versus a more delayed CT scan are discussed.     

Regulatory properties of brain glutamate decarboxylase (GAD): the apoenzyme of GAD is present principally as the smaller of two molecular forms of GAD in brain

The apoenzyme of glutamate decarboxylase [enzyme without bound cofactor, pyridoxal 5'-phosphate (pyridoxal-P)] serves as a reservoir of inactive glutamate decarboxylase (GAD) that can be activated when additional GABA synthesis is required. We have investigated which of two molecular forms of GAD is present as apoenzyme in synaptosomes and in cortex, caudate nucleus, hippocampus, and cerebellum of rat brain. Endogenous glutamate apodecarboxylase (apoGAD) was labeled by incubating extracts of synaptosomes or punches of each region with 32P-pyridoxal-P, followed by reduction with NaBH4, to link covalently the 32P-pyridoxal-P to GAD. Proteins were separated by SDS-PAGE. Punches from all four brain regions and forebrain synaptosomes contained two forms of GAD with apparent Mrs of 63 and 65 kDa as identified by immunoblotting with four antiGAD sera. Punches and synaptosomes contained a major 32P-pyridoxal-P-labeled band with an apparent Mr of 63 kDa that was stained on immunoblots by the antiGAD serum 1440 and the monoclonal antibody GAD-6, and a minor labeled band at 65 kDa that was stained by the 1440, 6799, and K2 antisera. Synaptosomes contained remarkably few other strongly labeled proteins, but punches contained several other labeled bands. Three additional lines of evidence indicate that the labeled 63-kDa protein is apoGAD: (1) it was purified by immunoaffinity chromatography with the GAD-1 monoclonal antibody; (2) it yielded one major labeled peptide when digested with chymotrypsin, and that peptide appeared identical in peptide-mapping experiments to the labeled active-site peptide isolated from chromatographically prepared rat brain GAD; and (3) its labeling was selectively blocked by 4-deoxypyridoxine 5'-phosphate, a competitive inhibitor of the binding of pyridoxal-P to GAD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dopamine differentially regulates dynorphin, substance P, and enkephalin expression in striatal neurons: in situ hybridization histochemical analysis.

Dopamine regulation of the levels of dynorphin, enkephalin, and substance P messenger RNAs in rat striatal neurons was analyzed with in situ hybridization histochemistry (ISHH). Relative levels of peptide mRNA expression in the patch and matrix compartments of the dorsolateral striatum were compared among control rats, rats treated for 10 d with apomorphine, rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic system, and rats with nigrostriatal dopaminergic lesions followed 2 weeks later by 10 d of apomorphine treatment. Image analysis of ISHH labeling demonstrated that the number of neurons expressing each peptide mRNA remained constant, whereas the relative level of peptide mRNA per neuron changed significantly, depending on the experimental treatment. Dynorphin mRNA expression increased following chronic apomorphine treatment: striatal patch neurons increased to an average of 100% above control values, whereas striatal matrix neurons showed only a 25% increase. Dynorphin mRNA expression decreased following 6-OHDA lesions: patch neurons showed an average 75% reduction in expression, whereas matrix neurons showed no significant change. In animals with 6-OHDA lesions followed by apomorphine treatment, both patch and matrix neurons showed an average increase in dynorphin expression of 300% above control levels. Changes in dynorphin mRNA levels with these treatments were matched by qualitative changes in dynorphin immunoreactivity both in the striatum and in striatonigral terminals in the substantia nigra. Neither substance P nor enkephalin mRNA levels showed a significant difference between the striatal patch and matrix compartments in any experimental condition (in the dorsolateral striatum). Substance P mRNA expression was increased an average of 50% after 10 d of apomorphine treatment and showed an average decrease of 75% following 6-OHDA lesions of the mesostriatal system. There was no significant change in the expression of substance P mRNA in striatal neurons compared to control values in rats with combined 6-OHDA lesion and apomorphine treatment. Enkephalin mRNA expression was not significantly altered by chronic apomorphine treatment but showed an average increase per cell of some 130% above control levels following 6-OHDA-induced lesions of the mesostriatal system. In animals with a 6-OHDA lesion and apomorphine treatment, enkephalin mRNA was also elevated but not significantly above the levels produced by the lesions alone. These data show that the expression of dynorphin, enkephalin, and substance P is differentially regulated by the mesostriatal dopaminergic system and, further, suggests that the mechanisms by which this regulation occurs may be different for the 3 peptide families.