Expression of class II major histocompatibility antigens on reactive astrocytes and endothelial cells within the gliosis surrounding metastases and abscesses.

To pursue the hypothesis that astrocytes may function as immunoregulatory cells, astrocytes within the reactive gliosis surrounding metastases and abscesses were examined for the expression of the class II major histocompatibility antigen HLA-DR. The tissue was analysed using single- and double-label avidin-biotin immunoperoxidase techniques employing monoclonal antibodies for HLA-DR (D1-12), macrophages (anti-Fc), T lymphocytes (2D3), glial fibrillary acidic protein (GFAP) and GFAP antiserum. Macrophages, astrocytes and T lymphocytes were present. The double label demonstrated HLA-DR on a large number of astrocytes. Taken together with evidence that astrocytes can release interleukin-1 and can present an antigen to lymphocytes, the finding of HLA-DR on these astrocytes supports their possible involvement in the cellular immune response.

Cultured human fetal astrocytes can be induced by interferon-gamma to express HLA-DR.

Interferon-gamma (IFN-gamma) modulates the expression of Class II major histocompatibility antigens (MHC), thus providing a potential regulatory mechanism for local immune reactivity in the context of MHC-restricted antigen presentation. Within the central nervous system (CNS), the expression of MHC Class II antigens has been demonstrated on human reactive astrocytes and glioma cells. In order to investigate the modulation of HLA-DR on normal astrocytes, two cell lines were grown from a 20-week-old fetal brain. In situ none of the fetal brain cells expressed HLA-DR as determined by immunohistology on frozen tissue sections. The two cell lines, FB I and FB II, expressed GFAP indicating their astrocytic origin. FB I was HLA-DR negative at the first tissue culture passages, but could be induced to express HLA-DR when treated with 500 U/ml IFN-gamma. FB II was spontaneously HLA-DR positive in the early passages, lost the expression of this antigen after 11 passages and could also be induced to express HLA-DR by IFN-gamma. The induction of HLA-DR expression was demonstrated both by a binding RIA and by immunoprecipitation using a monoclonal antibody (MAB) directed against a monomorphic determinant of HLA-DR. The HLA-DR alloantigens were determined on FB II cells after IFN-gamma treatment, by immunofluorescence and by cytotoxicity assays, and were shown to be DR4, DR6, Drw52, DRw53 and DQwl. These results show that human fetal astrocytes can be induced to express HLA-DR by IFN-gamma in vitro and support the concept that astrocytes may function as antigen-presenting cells.

Does vestibular stimulation activate thalamocortical mechanisms that reintegrate impaired cortical regions?

Caloric stimulation induced a transient reversal of multimodal hemispatial cognitive deficits in an 81-year-old woman with an acute left cerebral hemisphere stroke. The patient had unawareness of her right hand (asomatognosia), right-sided visual unawareness (hemineglect), aphasia and right-sided weakness (hemiplegia) prior to the stimulation. Transient improvements in impaired sensory, motor, linguistic and cognitive function developed within 30 s following application of the caloric stimulus and onset of horizontal nystagmus. The effect persisted for 3 min and ceased completely after 5 min. While several recent reports have described the capacity of caloric stimulation to transiently improve or reverse a wide range of attentional, cognitive and motor impairments, most examples are in right-hemisphere-damaged patients with long-standing brain injury. Typically, patients have been tested several months or years after the onset of the deficit. A possible mechanism for the temporary reintegration of multiple cognitive functions in this patient is discussed.

[Immunobiology of the normal and tumor astrocyte]. / Immunobiologie de l'astrocyte normal et tumoral.

Immunobiology of the normal and tumoral astrocytes studies interactions between these cells and the immune system. Their antigenic characterization defines 3 classes of antigens: glial antigens, tumor associated antigens (neuroectodermal and gliomatous) and lymphoid differentiation antigens which can be modulated by gamma interferon and other cytokines. Glioma associated antibodies could be used for radiolocalization of tumours and for immunotherapy. The enhancement or induction of the Major Histocompatibility Complex antigen expression by interferon gamma could enhance tumour-antigen presentation by glioma cells to helper and cytotoxic T cells and thus activate the host's immune response. The presence of oncogenes and their products in glioma cells, mainly growth factor receptors, brings new potential therapies using oncogenes products as tumoral markers or as targets for monoclonal antibodies blocking their mitogenic activity. Normal and tumoral astrocytes produce lymphokines: interleukin 1, interleukin 3, prostaglandin E as well as a suppressor factor inhibiting interleukin 2 mediated effects and probably responsible for the suppression of glioma infiltrating T cells. The interaction of astrocytes with several humoral factors related to the immune system and their capacity to function as antigen presenting cells underline their importance for immune reactions within the central nervous system.

Noninvasive microscopic evaluation of the intact living nephrotic kidney.

BACKGROUND: Tandem Scanning Confocal Microscopy (TSCM) is a new form of microscopy that allows one to noninvasively "optically section" into intact structures and record microscopic images in real-time. In this study, we have evaluated the ability of this new technology to distinguish histopathologic changes in unstained living kidneys that occur coincident with the onset of puromycin aminonucleoside-induced nephrosis. EXPERIMENTAL DESIGN: The rats were anesthetized and a laparotomy was performed to expose the kidneys. Using a TSCM equipped with a 24x water-immersion objective, we viewed and recorded real-time images of subcapsular living uriniferous tubules and glomeruli of puromycin aminonucleoside-induced nephrosis rats exhibiting different levels of proteinuria. RESULTS: TSCM revealed a variety of histopathologic changes in the puromycin aminonucleoside-induced nephrosis uriniferous tubules including dilation of proximal tubular lumens, loss of microvillous brush border, cellular debris in the tubule lumens, and focal regions of extensive tubular necrosis. Using the fluorescent probe carboxyfluorescein, we were able to demonstrate significant heterogeneity in the movement of this fluorescent probe through the uriniferous tubules (e.g., some tubules were completely blocked), and irregular patterns in flow of carboxyfluorescein through nephrotic glomeruli. CONCLUSIONS: These observations indicate that TSCM is capable of revealing a variety of histopathologic changes in unstained, intact, living kidneys. In addition, many of the histopathologic features of the uriniferous tubules revealed by TSCM are difficult or impossible to distinguish in biopsied samples of renal tissue.

The effect of menopause and perimenopause on the course of epilepsy.

PURPOSE: The purpose of this study was to obtain preliminary information about the effect of menopause and perimenopause on the course of epilepsy, and to determine whether seizure type, use of hormone-replacement therapy (HRT), or a history of catamenial seizure pattern would influence this course. METHODS: We performed a questionnaire study of women with epilepsy currently in menopause and perimenopause, requesting information regarding the course of their epilepsy and treatment. Statistical analysis was performed by using Pearson chi2 with 95% confidence limits. RESULTS: Forty-two menopausal women (ages 41-86 years) responded. Twelve subjects reported no change in seizures at menopause, 17 reported a decrease in seizure frequency, and 13 reported an increase. Sixteen (38%) took synthetic HRT. Sixteen (38%) additional subjects (having some overlap with the HRT group) reported having a catamenial seizure pattern before menopause. HRT was significantly associated with an increase in seizures during perimenopause (p = 0.001). A history of catamenial seizure pattern was significantly associated with a decrease in seizures at menopause (p = 0.013). Thirty-nine perimenopausal women (ages 38-55 years) responded. Nine subjects reported no change in seizures at perimenopause, five reported a decrease in seizure frequency, and 25 reported an increase. Eight (15%) subjects took synthetic HRT, and 28 (72%) reported having a catamenial seizure pattern before menopause. HRT had no significant effect on seizures; however, a history of catamenial seizure pattern was significantly associated with an increase in seizures at perimenopause (p = 0.02). CONCLUSIONS: These pilot data suggest that synthetic HRT may be associated with an increase in seizure frequency in menopausal women with epilepsy. A catamenial seizure pattern may be associated with seizure decrease during menopause but with an increase during perimenopause.

Measurement of pi(0)pi(0) production in the nuclear medium by pi(-) interactions at 0.408 GeV/c.

We report on an investigation of the (pi(-),pi(0)pi(0)) reaction by means of measurements of the pi(0)pi(0) invariant mass distributions from pi(-) interactions on H, D, C, Al, and Cu targets at p(pi(-)) = 0.408 GeV/c. The sharp, strong peak in the pi(+)pi(-) invariant mass near 2m(pi) reported by the CHAOS Collaboration is not seen in our pi(0)pi(0) data. However, we do observe a change in the shape of the pi(0)pi(0) invariant mass spectrum for the different targets, indicating that the pi(0)pi(0) interaction diminishes in the nuclear medium as represented by nuclei D, C, Al, and Cu, compared to hydrogen.

Dynamics of the pi(-)p-->pi(0)pi(0)n reaction for p(pi(-))<750 MeV/c.

Data are presented for the reaction pi(-)p-->pi(0)pi(0)n in the range from threshold to p(pi(-))=750 MeV/c. The systematics of the data and multipole analyses are examined for sensitivity to a f(0)(600) ("sigma") meson. A one-pion-exchange mechanism is found to be very weak, or absent. The reaction appears to become dominated by sequential pi(0) decays through the Delta(1232) resonance as the beam momentum increases, along with substantial interference effects from several competing mechanisms.

Determination of the quadratic slope parameter in eta-->3pi(0) decay.

We have determined the quadratic slope parameter alpha for eta-->3pi(0) to be alpha = -0.031(4) from a 99% pure sample of 10(6)eta-->3pi(0) decays produced in the reaction pi(-)p-->n(eta) close to the eta threshold using the Crystal Ball detector at the AGS. The result is four times more precise than the present world data and disagrees with current chiral perturbation theory calculations by about four standard deviations.