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Evolution of clonality and invasive behavior of Epstein-Barr virus immortalized lymphoblastoid cell lines in SCID mice brains.

BACKGROUND: Recently established Epstein-Barr virus immortalized lymphoblastoid cell lines express polyclonal immunoglobulins, are diploid, and grow into invasive tumors when injected intracerebrally into mice with severe combined immunodeficiency (SCID). It is unclear whether clonal selection of neurotropic cell lines occurs during long-term growth in the brain and the effect of this selection on brain invasiveness. EXPERIMENTAL DESIGN: Epstein-Barr immortalized lymphoblastoid cell lines from a normal Epstein-Barr negative donor were serially passaged seven times intracerebrally within groups of SCID/SCID CB 17 mice. Each cell line was injected into five or more animals during each passage. Clonality of the rescued cell lines, genotype, and brain invasiveness were examined. RESULTS: All mice developed extensive intracerebral lymphoproliferative disease within 10-18 days after injection. Intracerebral, subarachnoid, intraventricular, and perivascular lymphoid lesions were noted. Infiltrates were similar in all animals studied regardless of the passage number. Clonal B cell populations were detectable in lesions after the first passage by Southern blot hybridization using JH probe. Immunohistochemically, polyclonal tumors were seen initially, but after the fourth passage, monoclonal cytoplasmic immunoglobulin was predominantly expressed by all tumors. Minor bands seen in the early passages disappeared subsequently. Random chromosomal abnormalities appeared in the rescued cell lines after the third passage; however, after the sixth passage, the abnormalities became more consistent. Clonability in agarose was very low initially in both cell lines and increased significantly after the sixth passage. CONCLUSIONS: These experiments demonstrate that within the immunoprivileged conditions of the SCID mouse brain, the evolution of Epstein-Barr immortalized lymphocytes from polyclonal to oligo- and monoclonal cell lines with chromosomal abnormalities occurs very early. This evolution is not paralleled by increased invasiveness in vivo.

Animals

An anthropological perspective on the evolution and lateralization of the brain.

The purpose of this paper is to review the anthropological evidence relating to the cultural determinants of the right-hand first postaulted by Hertz in his classic study. Also a genetic/cultural conformity model of handedness is presented that postulates that the incidence of handedness in a society is held to result both from the genetic expression of handedness interacting with cultural pressures towards conformity. The evolutionary basis for the hemispheric functional organization into cognitive and perceptual hemispheric functions is discussed in terms of "right-handed dominant homozygotes, DD," "heterozygotes, DR," mixed-handers, and "left-handed recessive homozygotes, RR." The cross-cultural distribution of handedness provides support for this model since the more conforming agriculturalists as measured by the Asch Test have a significantly lower incidence of left-handedness (0.59%, 1.5% and 3.4%), while the more permissively socialized Eskimo and Arunta hunters, who are seen to be more independent on the Asch Test, have 11.3% and 10.5% left-handers, respectively. Also, due to the greater pressures for females to conform in agricultural societies, the incidence of female left-handedness in agricultural societies is 0% out of 330 female Ss, with 3.8%, 0.79%, and 2.5% in agricultural males, as contrasted with the Eskimo hunters who have 12.5% left-handed males and 10.3% left-handed females, showing no significant sex difference. A further Hong Kong-English study also supports the genetic/cultural conformity model with a significantly lower incidence of Hong Kong Chinese left-handers (RR: male = 2.7%, and female = 4.2%). The next section, concerned with the neonatal sex-hormone differentiation and lateralization processes, provides a neuropsychologic theory relating to spatial and linguistic skills that is relevant to the following section, which deals with relationships between laterality and cognitive style. The results are also presented for the Alaskan Eskimo in relation to hand, eye, auditory dominance and cognitive style. The analysis of Eskimo fixed-versus mixed-laterality data also confirms, as predicted, that both within and across a modality (e.g., right hand/right eye/right ear) fixed right-dominance Eskimo Ss are more field-independent than mixed-dominance Ss, while the fixed left-dominance Ss are the most field-dependent and have lower spatial skills. The discussion section reviews the papers relating to the genetic/conformity model of handedness, as well as laterality and cognitive style. The evolutionary adaptive significance of sex differences in gonadal differentiation and lateralization of the brain on spatial and linguistic skills are also reviewed. The conclusions are concerned with the implications for biosocial theory and the rapidly changing incidence of left-handedness due to accompanying changes in cultural pressures both within and across cultures.

Adult

Arteriovenous malformations. Locations and evolution in the fetal brain.

Almost all cerebral arteriovenous malformations in the fetus involve the vein of Galen, although occasionally they may involve the frontal area of the brain instead. In all reported cases arteriovenous malformations have presented some time after 30 weeks as a sonolucent oval lesion located in the midline behind the third ventricle. Previous scans have been normal. Evidence of high output failure such as cardiomegaly, enlarged neck veins, or hydrops predicts a poor outcome.

Aneurysm

Further observations on pineal brain sand formation and evolution in man.

Acervuli obtained from fragments of the human pineal glands of subjects of both sexes and age ranging from 23 to 87 years were analyzed by light microscopy after histochemical stains and by EDS-microanalysis. It was found that the sub-units and acervuli are positive to P.A.S., Alcian Blue pH 2.5, Gomori-Bargmann procedures for the presence of proteins, glycoproteins, proteoglycans and of the neurosecretory material in different layers of the sub-units and acervuli. We suppose that the increase of Mg++ in the sub-unit from the core to the periphery is responsible for the inhibition of following hydroxyapatite deposition and for growth. We suggest that the presence of glycoproteins and proteoglycans can represent the aggregation factor for bindings between disulphide bonds and calcium.

Adult

Temporal evolution of ischemic damage in rat brain measured by proton nuclear magnetic resonance imaging.

We studied the effect of focal cerebral ischemia on the "state" of brain water using proton nuclear magnetic resonance imaging. Focal cerebral ischemia was induced in five halothane-anesthetized rats via tandem occlusion of the left common carotid artery and the left middle cerebral artery. The proton transverse relaxation time, the proton density, and the water diffusion coefficient were measured at various times from the same region of brain tissue from 1.5 to 168 hours after occlusion. Early measurements indicated significant changes in the transverse relaxation time (p = 0.004) and water diffusion coefficient (p = 0.002) of ischemic brain tissue compared with a homologous region from the contralateral hemisphere. However, the transverse relaxation time, proton density, and water diffusion coefficient in ischemic brain tissue showed different temporal evolutions over the study period. Diffusion coefficient weighting was superior to relaxation time and proton density weighting for the visualization of early cerebral ischemia. Our data suggest that nuclear magnetic resonance imaging is sensitive in detecting changes in proton-associated parameters during early cerebral ischemia and confirm significant changes (p less than or equal to 0.01) in the temporal evolution of transverse relaxation times, proton densities, and diffusion coefficients following middle cerebral artery occlusion.

Animals

The theory of encephalization.

The theory of encephalization is developed from elementary dimensional requirements for the construction of a brain of given size. The basic assumption in the theory is that most of the brain in vertebrates is constructed as a series of mappings repeated at various levels. Encephalization is seen as a composite of an amplification factor for the repeated mappings (identical with the encephalization quotient EQ) and a factor associated with "added" tissue. The latter may be viewed as tissue that corresponds to new functions. The relation of the theory to allometric analysis is a relationship of theory to empirical estimation of "expected" brain size at a given body size. But body size is not fundamental to the theory. It is merely one of several possible sources of a measure of the area of a basic mapping, as it were, which is then subject to the amplification factor. Issues in the use of encephalization to assess behavioral capacities are reviewed briefly, as are the neurobiological correlates of encephalization and brain size.

Animals