Morphological features in human cortical brain microvessels after head injury: a three-dimensional and immunocytochemical study

We studied the morphology of cortical microvessels in the brains of 10 patients who had died after receiving a traumatic head injury (THI). Scanning electron microscopy (SEM) of vascular corrosion casts, confocal microscopy of histological sections after immunocytochemistry, and detection of apoptosis by terminal dUTP nick end labeling (TUNEL) were used. Microvascular casts showed an angioarchitectonic distribution that was defined as normal according to results obtained in a previous, nontraumatic series of subjects. However, when we compared them with previous works, the cast surface of some of the microvessels showed three types of morphological alterations: longitudinal folds, sunken surfaces with craters, and a significant flattening with reduction of lumen. The vessels that were primarily affected were the arterioles and capillaries of the middle and deep cortical vascular zones. Immunostaining with the monoclonal antibody MAS-336 against endothelial cells also showed the presence of longitudinal folds with a thinning of the vascular lumen, cytoplasmic round bodies, and a thickening of the endothelial cell membrane. The TUNEL technique revealed a positive staining of some endothelial cells. The structural alterations we observed indicate that microvessels undergo endothelial cell damage after THI. We suggest that this kind of lesion and the secondary functional injury to the blood-brain barrier (BBB) could play an important role in the development of the secondary lesions that these patients show in the subacute phase.     

Co-expression of B7-1 and ICAM-1 on tumors is required for rejection and the establishment of a memory response

Although the transfection of B7-1 cDNA into a few mouse tumor cell lines can induce anti-tumor T cell immunity, its expression alone is ineffective in many other tumor cell lines tested. We were interested to study what factors limit B7-1 co-stimulatory activity, and decided to investigate whether B7-1 requires the cooperation of ICAM-1 to provide the minimal co-stimulatory signal for establishing an efficient anti-tumor immunity. We show that the transfection of B7-1 cDNA into three ICAM-1⁺ (plasmocytoma J558L, T lymphomas EL-4 and RMA), but not into two ICAM-1^? tumor cell lines (adenocarcinoma TS/A and melanoma B16.F1), is sufficient to induce their complete rejection in syngeneic mice. The expression of ICAM-1 is necessary for the rejection of the B7 expressing tumors, since the primary response elicited by B7-1⁺ EL-4 and RMA clones expressing reduced levels of ICAM-1 is severely reduced. Furthermore, super-transfection of ICAM-1 cDNA into B7-1⁺ adenocarcinoma and melanoma clones optimizes their primary rejection. Histologic examination of transfected tumors reveals that B7-1 and ICAM-1 exert a potent pro-inflammatory activity. The intra-tumor infiltration is composed of both eosinophils and lymphomono-cytes, and is already massive 5 days after the tumor challenge. The primary rejection of the B7-1⁺ ICAM-1⁺ tumors depends critically on CD8⁺ T cells, natural killer cells and granulocytes, but is independent of CD4⁺ T cells. Remarkably, in addition to its effects on the early phases of the immune response, the co-expression of ICAM-1 and B7-1 on tumors is also necessary for the efficient induction of a memory response. In fact, only the primary challenge with B7-1⁺, ICAM-1⁺ tumor cells protects the majority of the mice from a second injection of parental tumor cells. Collectively, our findings indicate that B7-1 and ICAM-1 are fundamental components for triggering the primary rejection of tumors and establishing a protective memory response. These findings may help to define new strategies for the rational application of co-stimulation in tumor immunotherapy.     

Interleukin-10 haplotypes in Celiac Disease in the Spanish population

Background  

Celiac disease (CD) is a chronic disorder characterized by a pathological inflammatory response after exposure to gluten in genetically susceptible individuals. The HLA complex accounts for less than half of the genetic component of the disease, and additional genes must be implicated. Interleukin-10 (IL-10) is an important regulator of mucosal immunity, and several reports have described alterations of IL-10 levels in celiac patients. The IL-10 gene is located on chromosome 1, and its promoter carries several single nucleotide polymorphisms (SNPs) and microsatellites which have been associated to production levels. Our aim was to study the role of those polymorphisms in susceptibility to CD in our population.     

Virilizing mature ovarian cystic teratomas

 Three further cases of mature benign cystic teratomas of the ovary associated with virilization are added to the three previously reported in the literature. They were found in postmenopausal, obese, diabetic women aged 52, 61, and 67 years. The patients presented with hirsutism and voice changes and clitoromegaly was present in one. Testosterone and androstenedione levels were elevated but promptly regressed after removal of the tumours. Histologically, sheets of stromal luteinized cells were found peripherally at the interface between the neoplasm and ovarian tissue. Luteinization of ovarian stroma induced by an unknown factor related to diabetes mellitus is the origin of the virilization. Received: 8 January 1997 / Accepted: 28 February 1997     

Differential expression of stem cell mobilization-associated molecules on multi-lineage cells from adipose tissue and bone marrow

Our laboratory has characterized a population of stromal cells obtained from adipose tissue termed processed lipoaspirate cells (PLAs). PLAs, like bone-marrow derived mesenchymal stem cells (BM-MSCs), have the capacity to differentiate along the adipogenic, osteogenic, chondrogenic, and myogenic lineages, In order to better characterize these two multi-lineage populations, we examined the surface phenotype of both bone marrow and adipose tissue-derived cells from five patients undergoing surgery. PLA and BM-MSC cells were isolated, subcultivated, and evaluated for cell surface marker expression using flow cytometry. PLA and BM-MSC cells both expressed CD13, CD29, CD44, CD90, CD105, SH-3, and STRO-1. Differences in expression were noted for cell adhesion molecules CD49d (Integrin alpha4), CD54 (ICAM-1), CD34, and CD106 (VCAM-1). While markedly similar, the surface phenotypes of PLA and BM-MSC cells are distinct for several cell adhesion molecules implicated in hematopoietic stem cell homing, mobilization, and proliferation.     

High and low frequency transcutaneous electrical nerve stimulation inhibits nociceptive responses induced by CO2 laser stimulation in humans

The aim of the study was to evaluate the effects of transcutaneous electric nerve stimulation (TENS) on CO(2) laser evoked potentials (LEPs) in 16 normal subjects. The volar side of the forearm was stimulated by 10 Hz TENS in eight subjects and by 100 Hz TENS in the remainder; the skin of the forearm was stimulated by CO(2) laser and the LEPs were recorded in basal conditions and soon after and 15 min after TENS. Both low and high frequency TENS significantly reduced the subjective rating of heat stimuli and the LEPs amplitude, although high frequency TENS appeared more efficacious. TENS seemed to exert a mild inhibition of the perception and processing of pain induced by laser Adelta fibres activation; the implications of these effects in the clinical employment of TENS remain to be clarified.     

Dynamics of the junction between the medulla and the cervical spinal cord: An in vivo study in the sagittal plane by magnetic resonance imaging

Summary Sagittal sections of the brain-stem made by MRI reveal differences in the angle formed by the medulla and the cord. In order to study the normal mobility of this region of the CNS during flexion and extension of the head, sagittal MRI studies were made in the sagittal plane in 18 young volunteers. The volunteers were in dorsal decubitus with the cervical spine first flexed and then extended, with the movement localized to the cranio-cervical junction as far as possible. T1-weighted sequences were used, with body coils in 16 cases and surface coils in two. Measurements were related to global cranio-cervical range of movement, movement at the craniocervical junction and spino-medullary movement. Variations in the depth of the free space in front of the medulla, pons and spinal cord during movement were also noted. We also checked for downward shift of the lower part of the 4th ventricle and modification of the shape of the ventricle during flexion-extension. The global range of cranio-cervical movement was between 31 and 100° (average 63°). The range between the cranium and C1C2 was 4 to 39° (average 19°) and the spino-medullary range was from 1 to 32° (average 14°). During flexion, the free space narrowed in front of the pons 11 times, in front of the medulla 14 times and in front of the cervical cord 11 times. There was a downward shift of the lower part of the 4th ventricle during flexion in 4 cases but no change in shape was noted. Though this study is open to criticism from several aspects, it may be concluded that variations of the spino-medullary angle in the sagittal plane during flexion-extension do occur, that they are closely correlated with movements at the cranio-cervical junction, and that the spino-medullary junction moves forward during flexion.

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Dynamique de la jonction bulbomédullaire et de la moelle cervicale: Étude in vivo dans le plan sagittal en imagerie par résonance magnétique

Résumé Dans le but d'étudier la mobilité normale de la jonction bulbomédullaire durant la flexionextension de la tête, nous avons exploré en IRM dans le plan sagittal 18 jeunes volontaires. L'appareil Magniscan 0,15 Tesla a été utilisé avec des séquences de spin écho courtes, 16 fois en antenne corps et 2 fois en antenne de surface. Dans les limites de notre méthodologie, le secteur global de mobilité cervico-céphalique varie de 31 à 100° (moyenne 63°), le secteur de mobilité O-C1C2 varie de 4 à 39° (moyenne 19°), le secteur de mobilité bulbomédullaire varie de 1 à 32° (moyenne 14°). Lors de la flexion, l'espace libre diminue 11 fois devant la protubérance, 14 fois devant le bulbe et 11 fois devant la moelle cervicale. La partie basse du V4 s'abaisse dans 4 cas en flexion. Aucune modification de la forme du V4 n'a pu être notée. Bien que cette étude soit critiquable à bien des égards, nous pouvons affirmer: que les variations de l'angle bulbomédullaire dans le plan sagittal durant la flexion-extension de la tête sont effectives; qu'elles sont étroitement corrélées à celles de la charnière cranio-rachidienne; que durant le mouvement de flexion, la jonction bulbomédullaire se déplace en avant.

     

The orchestration of the sensory-motor systems: Clues from Neuropsychology

Research over the last several decades has led to clear and empirically tractable proposals about the representation of conceptual knowledge in the brain. Here we argue that there are already sufficient data from neuropsychology to strongly constrain extant hypotheses about the representation of conceptual knowledge. One constraint imposed by these neuropsychological data is that recognition of actions and understanding of objects do not necessarily depend on the ability to produce object-associated actions. This conclusion compels a reconsideration of the role played by motor planning and/or execution processes in action and object recognition and understanding.