Usefulness of magnetic motor evoked potentials in the surgical treatment of hemiplegic patients with intractable epilepsy.

Five hemiplegic patients with intractable epilepsy were studied with transcranial magnetic stimulation (TMS) before and after various surgical treatments. These patients had unilateral widespread cerebral lesions acquired at various times, including congenital, infantile and childhood injury. Motor evoked potentials (MEPs) of the abductor pollicis brevis (APB) muscles were simultaneously recorded on both sides following TMS of the motor cortex in the respective hemisphere using a figure-8 or circular coil. In all patients with congenital disease, the abolition of motor function in the affected hemisphere was estimated by magnetic MEPs, and the hemiplegia did not deteriorate after functional hemispherectomy (HS) was performed in two of them. In two patients with acquired disease, HS was not performed because it was shown by magnetic maps that the motor function in the affected hemisphere remained. Furthermore, it was shown by electric MEPs using subdural electrodes that a patient who had had encephalitis in early childhood had a reorganised motor area in the parietal cortex of the affected hemisphere. The present findings indicate that magnetic MEPs are a very useful non-invasive method of assessing whether the motor area in the affected hemisphere can be resected in hemiplegic patients with intractable epilepsy.     

Effects of Several Denervation Procedures on Distribution of Calcitonin Gene-Related Peptide and Substance P Immunoreactive in Rat Stomach

The effect of chemical deafferentation, vagotomy(VGX), and gangliosympathectomy (GSX) on the density offibers containing calcitonin gene-related peptide (CGRP)and substance P (Sub.P) in the rat gastric wall was studied. Chemical deafferentation bycapsaicin abolished the density of CGRP-immunoreactive(IR) fibers, not Sub.P-IR fibers. Ten days after VGX,the density of CGRP-IR or Sub.P-IR fibers in the mucosa was largely reduced, while no reductionof CGRP-IR and Sub.P-IR fibers was seen in submucosaland muscular layers. GSX significantly reduced thedensity of CGRP-IR fibers in the mucosa and caused a moderate decrease in the fibers in submucosaland muscular layers. Pretreatment with6-hydroxydopamine, a neurotoxin for noradrenergicnerves, did not affect the density of CGRP-IR fibers inthe gastric wall. The density of Sub.P-IR fibers in thegastric wall was not affected by GSX. These studiesindicate that the CGRP-IR and Sub.P-IR fibers in themucosa are susceptible to extrinsic nerve denervation compared with those in the submucosa and musclelayers, that a major portion of the CGRP-IR fibers inthe mucosa is of both vagal and spinal origin, and thata major portion of the Sub.P-IR fibers in the mucosa is of vagal origin. Furthermore, thepresent results support that CGRP-IR fibers, notSub.P-IR fibers, in the rat stomach arecapsaicin-sensitive.     

Transient Brain Ischaemia Provokes Ca2+, PIP2 and Calpain Responses Prior to Delayed Neuronal Death in Monkeys

To clarify the mechanism of postischaemic delayed cornu Ammonis (CA)-1 neuronal death, we studied correlations among calpain activation and its subcellular localization, the immunoreactivity of phosphatidylinositol 4,5-bisphosphate (PIP₂) and Ca²⁺ mobilization in the monkey hippocampus by two independent experimental approaches: in vivo transient brain ischaemia and in vitro hypoxia-hypoglycaemia of hippocampal acute slices. The CA-1 sector undergoing 20 min of ischaemia in vivo showed microscopically a small number of neuronal deaths on day 1 and almost global neuronal loss on day 5 after ischaemia. Immediately after ischaemia, CA-1 neurons ultrastructurally showed vacuolation and/or disruption of the lysosomes. Western blotting using antibodies against inactivated or activated μ-calpain demonstrated μ-calpain activation specifically in the CA-1 sector immediately after ischaemia. This finding was confirmed in the perikarya of CA-1 neurons by immunohistochemistry. CA-1 neurons on day 1 showed sustained activation of μ-calpain, and increased immunostaining for inactivated and activated forms of μ- and m-calpains and for PIP₂. Activated μ-calpain and PIP₂ were found to be localized at the vacuolated lysosomal membrane or endoplasmic reticulum and mitochondrial membrane respectively, by immunoelectron microscopy. Calcium imaging data using hippocampal acute slices showed that hypoxia-hypoglycaemia in vitro provoked intense Ca²⁺ mobilization with increased PIP₂ immunostaining specifically in CA-1 neurons. These data suggest that transient brain ischaemia increases intracellular Ca²⁺ and PIP₂ breakdown, which will activate calpain proteolytic activity. Therefore, we suggest that activated calpain at the lysosomal membrane, with the possible release of biodegrading enzyme, will cause postischaemic CA-1 neuronal death.     

C3 Deposition in IgA Nephropathy in Children and Adolescents

The aim of this study was to assess the significance of C3 deposition in IgA nephropathy in children and adolescents. One hundred and two patients aged 5–21 years (57 male and 45 female) were studied. The findings of C3 deposition were classified into 8 groups by immunofluorescent (IF) pattern and intensity as follows: group MC3+ (N = 12): mesangiocapillary pattern and 3+ in intensity; group MC2+ (N = 13): mesangiocapillary and 2+; group MC1 + (N = 4): mesangiocapillary and 1 +; group M3+ (N = 11): mesangial and 3+; group M2+ (N = 24): mesangial and 2+; group M1 + (N=18): mesangial 1 +; group S (N = 12): only segmentally positive; and group N (N = 8): negative. Histological changes were scored semiquantitatively as an activity index (cellular proliferation, necrosis, interstitial cell infiltration, and cellular crescents) and a chronicity index (mesangial sclerosis, segmental and global glomerular sclerosis, fibrous crescents, adhesion and tubulo-interstitial change). IF findings were scored semiquantitatively and laboratory findings were also studied. The following results were obtained: 1) The scores of total activity index in MC groups were higher than in the M, S or N groups, and the greater the degree of C3 deposition, the higher the score; 2) Such result was not evident in the chronicity index; 3) High IF scores of IgG and IgM were found in the MC3+ and MC2+ groups; 4) Hematuria was more severe in MC3+ and MC2+ than in other groups, and proteinuria was more prominent in the MC than other groups. Thus the degree of C3 deposition was parallel with histological activity and urinary findings.     

An antigen-independent contact mechanism as an early step in T cell- proliferative responses to dendritic cells

Dendritic cells bearing antigen efficiently aggregate and stimulate antigen-specific T cells. We describe an experimental model in which an initial, apparently antigen-independent binding step is followed by ligation of the TCR. The model is the polyclonal response to mAb to the CD3 portion of the TCR complex. Epidermal and thymic dendritic cells utilize low levels of Fc receptors to present the anti-CD3 mAb and induce mitogenesis. Within 3 h of coculture, most of the dendritic cells have formed clusters with the resting T lymphocytes, and these clusters are the site for subsequent DNA synthesis and cell growth. However, the binding of dendritic cells to T cells proceeds as efficiently in the absence of anti-CD3 as in its presence, and anti-FcR mAb does not block. CD3 and Fc receptors are essential for the subsequent mitogenesis response in dendritic-T cell clusters. Because an exogenous ligand for the TCR does not seem to be required for the extensive polyclonal clustering of resting lymphocytes to dendritic cells, we suggest that an antigen-independent mechanism mediates the initial interaction. This clustering seems essential for T cell growth since we do not detect, in two-chamber experiments, soluble lymphocyte-activating factors that originate from dendritic-T cell aggregates and that activate anti-CD3-coated T cells.     

Haloperidol metabolism in psychiatric patients: importance of glucuronidation and carbonyl reduction.

In 39 patients who received haloperidol regularly we measured plasma concentrations of haloperidol glucuronide (HAL-GL), reduced haloperidol glucuronide (RHAL-GL), haloperidol (HAL), reduced haloperidol (RHAL), and HAL reductase activity in red blood cells. Plasma HAL-GL concentrations were significantly higher than HAL, RHAL, or RHAL-GL concentrations. Concentration ratios of total glucuronide to nonglucuronide and RHAL/HAL ratios were calculated as indices of glucuronidation and reduction capacity in each patient. The plasma glucuronidation ratios showed a significant negative correlation (r = -0.63, p less than 0.001) with the dose, while the reduction ratios showed a positive correlation (r = 0.75, p less than 0.001). No correlations were found between the HAL reductase activity in red blood cells and either the dose or RHAL/HAL. Based on these findings we suggest that glucuronidation of HAL is the major metabolic pathway of HAL in humans and its activity is important in determining steady-state plasma HAL concentrations. Glucuronidation may also be a major contributing factor in the interindividual variability of HAL metabolism.