Vasogenic edema on MELAS: a serial study with diffusion-weighted MR imaging

The authors performed a serial study of a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome (MELAS) who presented with diffusion-weighted MRI (DWI). DWI demonstrated a higher apparent diffusion coefficient in the lesion than in the control region during the acute stage of stroke. Vasogenic edema is present in stroke-like episodes in MELAS.     

Origin of the "N10" stationary-field potential after median nerve stimulation.

The scalp far-field potentials after median nerve stimulation at the wrist consist of P9, P11, P13, and P14 positive components. Earlier, Emerson et al. (1984) identified the "N10" negative potential in-between the P9 and P11 and claimed that this was not merely a passive return to the baseline after the P9 positive deflection but a distinct component reflecting a proximal brachial plexus volley. They thought N10 was a far-field potential having widespread distribution with a fixed latency. In this study we found that N10 was of higher amplitude after median nerve stimulation at the elbow than after stimulation at the wrist. Indeed the N10 latency was fixed from the lower anterior neck to the scalp, and its amplitude was maximum at the anterior lower neck. The latency of N10 was about 0.3 milliseconds longer than the Erb's potential and 0.15 milliseconds longer than the potential recorded from the lateral neck on the side of stimulation. The N10 amplitude increased in parallel with increased stimulus intensity. In order to explore the origin of the N10 stationary field potential, we designed a paired stimuli paradigm applied to the wrist (S1) and to the elbow (S2). The interstimulus interval between S and S2 was adjusted so that the timing of S2 was immediately after the traveling impulse produced by the S1 stimulus as it passed through the S2 stimulus site. This technique allowed stimulation of the anterior interosseous nerve selectively at the elbow while the median nerve originating from the wrist was undergoing refractory period. The response of (S1 + S2) - S1 showed only the N10 with absence of cervical and cortical responses, implying that N10 was activated, predominantly by the interosseous nerve, i.e., an antidromic motor volley, when the median nerve was stimulated at the elbow.     

Influence of antigenic forms and adjuvants on the IgG subclass antibody response to Aujeszky's disease virus in mice.

The influence of antigenic forms of Aujeszky's disease virus (ADV) and adjuvant types on the production of IgG subclass antibodies in mice was investigated. Particulate antigen, inactivated ADV, alone induced IgG1 and lower IgG2a antibody production, while the antigen adsorbed onto aluminum phosphate gel (alum) enhanced IgG1 antibody production but suppressed IgG2a antibody production as well as solubilized ADV antigen adsorbed onto alum. QS21 saponin purified from Quillaja saponaria promoted the production of IgG1 and IgG2a antibodies in a large extent against the both particulate and soluble antigens, while this saponin has strong hemolytic activity. Lablaboside F saponin isolated from Dolichos lablab without hemolytic activity, also induced the production of large IgG1 and little IgG2a antibody against both antigens. Oil-based adjuvant, ISA70 of water-in-oil type and ISA25 of oil-in-water type, increased IgG1 and IgG2a antibodies against the both soluble and particulate antigens, whereas a combination of ISA25 and soluble antigen reduced IgG2a antibody response. These results indicate that IgG1 antibody production was not suppressed by a combination of antigenic form and adjuvant type, however, IgG2a antibody production was influenced.     

E5531, a synthetic non-toxic lipid A derivative blocks the immunobiological activities of lipopolysaccharide.

1. The major pathological responses to Gram-negative bacterial sepsis are triggered by endotoxin or lipopolysaccharide. As endotoxin is shed from the bacterial outer membrane, it induces immunological responses that lead to release of a variety of cytokines and other cellular mediators. As part of a program aimed at developing a therapeutic agent for septic shock, we have developed E5531, a novel synthetic lipopolysaccharide antagonist. 2. As measured by release by tumour necrosis factor-alpha, human monocytes or whole blood can be activated by lipopolysaccharide, lipid A, and lipoteichoic acid (from Gram-positive bacteria). E5531 potently antagonizes activation by all these agents while itself being devoid of agonistic activity. 3. The inhibitory activity of E5531 was dependent on time of addition. When 10 nM E5531 was added simultaneously with lipopolysaccharide or 1 - 3 h before addition of lipopolysaccharide, production of tumour necrosis factor-alpha was inhibited by more than 98%. The addition of E5531 1 h after lipopolysaccharide reduced the efficacy of E5531 by 47%. 4. Antagonistic activity of E5531 was specific for lipopolysaccharide as it was ineffective at inhibiting interferon-gamma mediated NO release of RAW 264.7 cells, phorbor 12-myristate 13-acetate stimulated superoxide anion production in human neutrophils, concanavalin A stimulated mitogenic activity in murine thymocytes and tumor necrosis factor-alpha induced E-selectin expression in human umbilical vein endothelial cells. 5. E5531 as well as MY4, an anti-CD14 antibody, inhibited radiolabelled lipopolysaccharide binding in human monocytes. 6. These results support our contention that E5531 is a potent antagonist of lipopolysaccharide-induced release of tumour necrosis factor-alpha and other cellular mediators and may be an effective therapeutic agent for human septic shock due to Gram-negative bacteria.     

Delayed administration of ethyl eicosapentate improves local cerebral blood flow and metabolism without affecting infarct volumes in the rat focal ischemic model.

The objective of this study was to assess whether delayed administration of ethyl eicosapentate has a favorable effect on cerebral blood flow and metabolism in rats suffering from cerebral infarction. Adult male Sprague-Dawley rats weighing 250-300 g were used. Left middle cerebral artery occlusion was induced for 2 h. After 24-h reperfusion, rats were treated with ethyl eicosapentate (100 mg kg(-1); ethyl eicosapentate treated) or saline (saline treated) by gavage, once a day for 4 weeks. After 4 weeks, local cerebral blood flow and local cerebral glucose utilization were measured autoradiographically, and infarction size was measured. In the ischemic side, the local cerebral blood flow and local cerebral glucose utilization values in the parietal cortex and the lateral caudoputamen, which constituted the ischemic core, were equivalent to zero in both groups. The peri-infarcted areas, i.e., the frontal cortex and medial caudoputamen, were significantly higher in the ethyl eicosapentate treated group than the saline treated group. In the non-ischemic side, ethyl eicosapentate treated group had a tendency to improve local cerebral blood flow and local cerebral glucose utilization values in a medial caudoputamen. These results suggest that ethyl eicosapentate treatment may be beneficial for maintaining cerebral circulation and metabolism except for infarction area after cerebral infarction.     

Inhibition by alkylamines of NADPH oxidase through blocking the assembly of enzyme components.

Alkylamines inhibit NADPH oxidase both in intact neutrophils and in a cell-free system. The aim of this study was to examine the mechanism underlying this inhibitory effect. Among alkylamines with different chain lengths, the C12 compound (laurylamine) showed the greatest inhibitory effect on the cell-free NADPH oxidase activity induced by arachidonic acid (AA) in the presence of GTPgammaS. The inhibition was overcome by further addition of AA, and it was observed irrespective of whether laurylamine was added before or after the enzyme activation by AA. When added prior to the enzyme activation, laurylamine blocked translocation to the membrane of all three cytosolic components (p47-phox, p67-phox and rac) in a cell-free translocation assay. When added after the activation, laurylamine released only rac from the membrane. Laurylamine did not inhibit the reduction of cytochrome c by xanthine oxidase, suggesting that it does not have superoxide-scavenging activity. These results indicate that laurylamine inhibits both the activation process of NADPH oxidase and the activated enzyme itself by blocking the assembly of the oxidase components.     

G-CSF accelerates the cell-cycling of hematopoietic progenitor cells and abrogates the deceleration by TNF alpha

We examined the effects of granulocyte colony-stimulating factor (G-CSF) on cell-cycling of hematopoietic progenitors in serum-free methylcellulose clonal cultures. Serial observations of the cultures showed hastening of growth of colonies by G-CSF, as determined by evaluating the time for individual colonies of 20 cells to reach 40 cells. G-CSF did not affect the incidence of proliferating cells in each developing colony. Cell-cycle analysis revealed that addition of G-CSF to cultures led to a decrease in the percentage of cells in the G1 phase of the cell-cycle, thereby indicating that G-CSF can modulate the cell-cycle of hematopoietic progenitors mainly by shortening the period of the G1 phase. Tumor necrosis factor alpha (TNF alpha) exerted opposite effects on cell-cycling of hematopoietic progenitors to those seen with G-CSF. G-CSF abolished the inhibitory effects of TNF alpha on the cell-cycling of hematopoietic progenitors. These observations indicate positive and negative regulatory roles of C-CSF and TNF alpha, respectively, and their interactions in the regulation of cell-cycling of hematopoietic progenitors.     

Kinetics of d-tubocurarine disposition and pharmacologic response in rats

After bolus intravenous dosing of d-tubocurarine (d-TC) to rats, the twitch heights of the tibialis anterior muscle indirectly stimulated were followed, and its decrease was defined as pharmacologic response of d-TC. The relation between dose and response intensity was found to be well described with Hill's equation. According to a theory proposed by Smolen, Hill's equation was also applicable to the biophase d-TC concentration-response relation; the time courses of the relative biophase d-TC concentration indicated linear kinetics with dose levels 0.15 mg/kg and the occurrence of dose-dependent disposition with 0.30 mg/kg. After bolus i.v. dosing of³H-d-TC, plasma d-TC concentration obeyed a dose-independent two compartment model with doses 0.15mg/kg, but not with 0.30 mg/kg. This finding matched the above estimated with pharmacologic data. The active metabolite was not found in plasma and urine. The extent of d-TC plasma protein binding was independent of the wide range of plasma levels and its mean (±SD) value was 30.5 (±3.8). Plasma d-TC levels and pharmacologie response intensity were well correlated by Hill's equation and a three compartment model (the general two and the biophase compartments) in the dose range 0.15 mg/kg.This work was presented at the First Japanese-American Symposium on Pharmacokinetics and Biopharmaceutics, Tokyo, July 1981, which was held in memory of Dr. Sidney Riegelman.     

MR findings of posterior fossa hemangioblastomas.

MR findings of five posterior fossa hemangioblastomas were reported. In the cystic type, a cyst was low intensity on T1WI and high intensity on T2WI. Mural nodule was clearly enhanced by Gd-DTPA. In the solid type, the tumor was shown as an isointense lesion on T1WI and as high intensity on T2WI, but it was markedly and homogeneously enhanced by Gd-DTPA. Multiple extremely low-intensity serpentine "flow void" signs, indicating afferent and efferent vessels, were observed within or around the tumor. These were characteristic pictures in this tumor.