H2 superexcited states: experimental and theoretical characterization of their competing decay-channel fluorescence, dissociation, and ionization.

The absolute cross sections for the competing decay channels fluorescence, dissociation, and ionization of photoexcited long-lived superexcited H(2) molecular levels have been measured from the ionization threshold of H(2) up to the H(1s)+H(n=3) dissociation limit. The total and partial natural widths of these levels have been determined. Good agreement is found with first principles calculations carried out by multichannel quantum defect theory. The calculations reproduce the balance between the competing decay processes as well as its substantial level-to-level evolution.

Intramolecular electron scattering and electron transfer following autoionization in dissociating molecules.

Resonant Auger decay of core-excited molecules during ultrafast dissociation leads to a Doppler shift of the emitted electrons depending on the direction of the electron emission relative to the dissociation axis. We have investigated this process by angle-resolved electron-fragment ion coincidence spectroscopy. Electron energy spectra for selected emission angles for the electron relative to the molecular axis reveal the occurrence of intermolecular electron scattering and electron transfer following the primary emission. These processes amount to approximately 25% of the resonant atomic Auger intensity emitted in the studied transition.

Sudden interchannel interaction in the Tl 6p ionization above the 5d threshold

The linear magnetic dichroism in the angular distribution of Tl 5d and 6p photoelectrons and their dynamical spin polarization have been measured between hnu = 30 and 50 eV. In contrast to the Xe 5p photoionization at the 4d threshold, our results show that above the Tl 5d threshold strong interchannel coupling effects induce a sudden increase in the asymptotic phase difference of the s and d waves for the Tl 6p ionization. This shows that the valence excitation is different for resonant (Xe 4d) and nonresonant (Tl 5d) excitation from subvalence shells.

In vivo relationship of interleukin-2 and soluble IL-2 receptor to blood-brain barrier impairment in patients with active multiple sclerosis.

Interleukin (IL)-2 has well-recognized effects on cerebral endothelial cells and, therefore, may mediate disruption of the blood-brain barrier in patients with multiple sclerosis (MS). To evaluate the in vivo relationship of the IL-2 system to blood-brain barrier impairment in MS, levels of IL-2 and soluble IL-2 receptors (sIL-2R) in cerebrospinal fluid (CSF) and serum samples from 50 patients with active MS and 49 controls were correlated with values of the CSF to serum albumin ratio. Intrathecal levels of IL-2 and sIL-2R were significantly higher in MS compared with the control groups and correlated with albumin ratios in MS patients. Intrathecal levels of IL-2 and sIL-2R also correlated with the degree of barrier damage in these patients. It is suggested that intrathecal levels of IL-2 and sIL-2R are related to barrier impairment in MS and may be important in understanding some of the pathological changes of this condition.

Determination of interleukin-2 in cerebrospinal fluid by a sensitive enzyme-linked immunosorbent assay.

A sensitive technique was developed for the quantitative detection of intrathecal production of interleukin-2 (IL-2). Concentrations of IL-2 in paired cerebrospinal fluid (CSF) and serum samples were measured by an enzyme-linked immunosorbent assay using a monoclonal antibody and an affinity purified polyclonal antibody. The assay produced a linear response with respect to IL-2 concentration, and could readily detect levels of IL-2 as low as 1.5 international units/ml. Concentrations of IL-2 in CSF and serum samples were standardised by calculating their ratio to albumin concentration in order to correct for passive transudation of IL-2 across blood-CSF barriers. CSF IL-2/albumin ratios higher than concomitant serum ratios were considered indicative of intrathecal IL-2 production. The technique provides a sensitive, specific, and reproducible method for the determination of in vivo synthesis of IL-2 within the central nervous system.

Importance of intrathecal synthesis of IgD in multiple sclerosis. A combined clinical, immunologic, and magnetic resonance imaging study.

There is increasing evidence that soluble IgD has a certain role in the humoral immune response within the central nervous system. We report herein the results of a combined clinical, magnetic resonance imaging, and immunopathologic study to determine the clinical importance of intrathecal IgD synthesis. Intrathecal synthesis of IgD (detected through the calculation of index values) was studied in 64 patients with multiple sclerosis and in 50 neurologic control patients and normal subjects. Locally secreted IgD was detected in 30% of patients with clinically active multiple sclerosis, including two in whom magnetic resonance images of brain and spinal cord were normal and who had no evidence of intrathecal IgG synthesis. No intrathecal IgD production was detected in patients with clinically stable multiple sclerosis or those suffering from chronic progressive multiple sclerosis, while it significantly correlated with the interval from the last relapse and with the total duration of the disease process in patients with relapsing, remitting multiple sclerosis. Intrathecal IgD synthesis also correlated with the degree of cerebrospinal fluid pleocytosis and with the presence of free kappa and lambda light chain bands in cerebrospinal fluid. Present results supplement and expand earlier data and suggest that intrathecally secreted IgD is a putatively important part of the immune response in clinically active relapsing, remitting multiple sclerosis.

Significance of CSF immunoglobulins in monitoring neurologic disease activity in Behçet's disease.

We examined the intrathecal production of immunoglobulins (Ig) G, A, and M in 16 patients with Behçet's disease, 13 of whom have CNS involvement, and in 40 neurologic controls. Oligoclonal IgA and IgM bands were mainly detected in CSF samples from patients with active neuro-Behçet's disease and were documented to disappear when neurologic manifestations remit. Oligoclonal IgG bands, however, were not related to disease activity and were also found in some neurologic controls. High immunoglobulin index values were detected in both active and quiescent diseases and were high in some patients with impaired blood-CSF barriers. The study presented here demonstrates that CSF oligoclonal IgA and IgM may be helpful in monitoring CNS disease activity in neuro-Behçet's and could be useful in understanding the pathogenesis of this disease.

Intrathecal immune response in patients with the post-polio syndrome.

BACKGROUND: The syndrome of progressive muscular atrophy decades after acute paralytic poliomyelitis (post-polio syndrome) is not well understood. The theory that physiologic changes and aging cause the new weakness does not explain the immunologic abnormalities reported in some patients. An alternative explanation is persistent or recurrent poliovirus infection. METHODS: We assessed the intrathecal antibody response to poliovirus and intrathecal production of interleukin-2 and soluble interleukin-2 receptors in 36 patients with the post-polio syndrome and 67 controls (including 13 who had had poliomyelitis but had no new symptoms and 18 with amyotrophic lateral sclerosis). Intrathecal antibody responses to measles, mumps, herpes simplex, and varicella zoster viruses were also determined. RESULTS: Oligoclonal IgM bands specific to poliovirus were detected in the cerebrospinal fluid of 21 of the 36 patients with the post-polio syndrome (58 percent) but in none of the control group (P less than 0.0001). In quantitative studies there was evidence of increased intrathecal synthesis of IgM antibodies to poliovirus only among the patients with the post-polio syndrome; there was no increased synthesis of IgM to measles, mumps, herpes simplex, or varicella zoster viruses. The patients with post-polio syndrome had significantly higher mean (+/- SD) (cerebrospinal fluid levels of interleukin-2 and soluble interleukin-2 receptors than the controls (8.1 +/- 5.3 vs. 1.4 +/- 0.8 U per milliliter and 159.6 +/- 102.9 vs. 10.7 +/- 6.2 U per milliliter, respectively). The intrathecal synthesis of IgM antibodies to poliovirus correlated with the cerebrospinal fluid concentrations of interleukin-2 (P less than 0.0005) and soluble interleukin-2 receptors (P less than 0.001). CONCLUSIONS: An intrathecal immune response against poliovirus is present in many patients with the post-polio syndrome. In some of these patients the recrudescence of muscle weakness may be caused by persistent or recurrent infection of neural cells with the poliovirus.

Association between tumor necrosis factor-alpha and disease progression in patients with multiple sclerosis.

BACKGROUND: Cachectin, or tumor necrosis factor-alpha (TNF-alpha), is a principal mediator of the inflammatory response and may be important in the pathogenesis and progression of multiple sclerosis, an inflammatory disease of the central nervous system. METHODS: In a 24-month prospective study, we used a sensitive enzyme-linked immunosorbent assay to determine levels of TNF-alpha in cerebrospinal fluid and serum in 32 patients with chronic progressive multiple sclerosis and in 20 with stable multiple sclerosis and 85 with other neurologic diseases. An attempt was made to relate TNF-alpha levels with the degree of disability of the patients with multiple sclerosis and with their neurologic deterioration during the 24 months of observation. RESULTS: High levels of TNF-alpha were found in the cerebrospinal fluid of 53 percent of the patients with chronic progressive multiple sclerosis and in none of those with stable multiple sclerosis (P less than 0.001). TNF-alpha was detected in the cerebrospinal fluid of 7 percent of the controls (P less than 0.01) with other neurologic disease. In patients with chronic progressive multiple sclerosis, mean TNF-alpha levels were significantly higher in the cerebrospinal fluid than in corresponding serum samples (52.41 vs. 11.88 U per milliliter; range, 2 to 178 vs. 2 to 39; P less than 0.001). In these patients, cerebrospinal fluid levels of TNF-alpha correlated with the degree of disability (r = 0.834, P less than 0.001) and the rate of neurologic deterioration (r = 0.741, P less than 0.001) before the start of the study. Cerebrospinal fluid levels also correlated with the increase in neurologic disability after 24 months of observation (r = 0.873, P less than 0.001). CONCLUSIONS: These data provide evidence of intrathecal synthesis of TNF-alpha in multiple sclerosis and suggest that the level of TNF-alpha in cerebrospinal fluid correlates with the severity and progression of the disease. Our results suggest that TNF-alpha may reflect histologic disease activity in multiple sclerosis and could be used to monitor outcomes or responses to therapy.

The relationship of interleukin-2 and soluble interleukin-2 receptors to intrathecal immunoglobulin synthesis in patients with multiple sclerosis.

The in vivo relationship of interleukin-2 (IL-2) to the local humoral immune response within the central nervous system (CNS) in patients with multiple sclerosis (MS) is hitherto largely unknown. Intrathecal levels of IL-2 and soluble IL-2 receptors (sIL-2R) were correlated to the local CNS synthesis of immunoglobulin G, A, D, and M isotypes in 70 patients with clinically definite MS. Levels were also determined in 19 normal control subjects to establish normal reference limits. High cerebrospinal fluid levels of IL-2 and sIL-2R were detected mainly in patients with acute relapsing-remitting MS and were significantly higher than corresponding serum levels. Intrathecal levels of IL-2 significantly correlated with local CNS synthesis of IgD and IgM, while no correlation was found with either IgG or IgA. Similarly, intrathecal sIL-2R levels significantly correlated with local CNS production of IgD and IgM, but not IgG or IgA. These findings further extend previous reports and also suggest that IL-2 and sIL-2R are involved in the early intrathecal humoral immune response in MS.