Endothelium-dependent and -independent mechanisms of action of acetylcholine in monkey and dog isolated arteries

In helical strips of monkey coronary and mesenteric arteries and dog mesenteric arteries partially contracted with prostaglandin (PG)F2 alpha, the mechanism of action of acetylcholine (ACh) has been analyzed by the use of pharmacological antagonists and by the endothelium-derived relaxing factor (EDRF) bioassay and the 6-keto PGF1 alpha radioimmunoassay. In conclusion, ACh releases vasodilator substance(s) from endothelium (EDRF) and also PGs from subendothelial tissues. Vasoconstrictor PGs appear to counteract the dilator action of EDRF in monkey coronary arteries, whereas vasodilator PG, possibly PGI2, appears to facilitate the relaxation caused by EDRF in monkey and dog mesenteric arteries.     

Correlation between renal function and pharmacokinetic parameters of inorganic fluoride following sevoflurane anesthesia

We studied the correlation between renal function and pharmacokinetic parameters of inorganic fluoride following sevoflurane anesthesia. In 30 neurosurgical patients aged 40–70 years, anesthesia was induced with midazolam and sevoflurane and maintained with sevoflurane and nitrous oxide in oxygen. Serum and urine inorganic fluoride (F⁻) levels and β₂-microglobulin (BMG), blood urea nitrogen (BUN), and serum creatinine (Cr) were measured during and after anesthesia. The decrease rate of serum F⁻ level and the area under the curve (AUC) of serum F⁻ were calculated. Correlations among sevoflurane dosage, duration of administration, peak serum F⁻ level, AUC, the decrease rate of serum F⁻ level, and the maximum values in BUN, Cr, and urine BMG during the study were investigated. Urine BMG increased significantly after surgery but returned to the preoperative level in a week. BUN, Cr, and serum BMG remained within normal ranges during the study. Sevoflurane dosage and duration of administration were significantly correlated with AUC and the maximum value of urine BMG, but not with the peak serum F⁻ level or the decrease rate of serum F⁻. AUC was significantly correlated with the maximum value of urine BMG. In sevoflurane anesthesia, sevoflurane dosage, duration of administration, and AUC affected urine BMG level, but not peak serum F⁻.     

The persistence of interleukin-6 is regulated by a blood buffer system derived from dendritic cells

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Poliovirus infection of established human blood cell lines: relationship between the differentiation stage and susceptibility of cell killing

The replication of type 1 poliovirus in 13 established human blood cell lines differing in the differentiation stage and cell lineage was investigated. Three T (CCRF-CEM, CCRF-HSB-2, and Molt-3) and three B (Raji, CCRF-SB, and RPMI 8226) cell lines showed no cytopathic effects (CPE) or virus production. CPE associated with virus production were detected in the other seven cell lines: HL-60, ML-1, and KG-1 (granulocytic lineage), U-937 and THP-1 (monocytic lineage), K-562 (erythroid lineage), and Molt-4 (T cell lineage). These susceptible cell lines greatly differed in the speed at which the CPE progressed. The progression of CPE was faster in relatively well-differentiated cell lines such as HL-60 and U-937, independently of the multiplicity of infection, than in less differentiated cell lines such as K-562, KG-1, and THP-1. Thus, for the same lineage, the speed at which CPE progressed became proportionally higher with subsequent differentiation stages. In the K-562 cell culture, CPE were not observed until at least 5 days postinfection (p.i.), while more than 80% of HL-60 cells were killed within 3 days p.i. There were no significant differences between infected HL-60 and K-562 cells in the efficiency of infection determined at 8 hr p.i. by the indirect immunofluorescent technique, the rate of virus growth, or the amount of viral capsid protein synthesized. This indicated that there were similar viral replication cycles in the two cell lines. These observations suggest that the killing function of the virus is expressed more slowly in K-562 cells than in HL-60 cells.     

Comparison of hippocampal synaptosome proteins in young-adult and aged rats

The hippocampus is important in learning and memory functions but its ability to aid in these functions declines during aging. In this study, we examined hippocampal proteins whose expressions changed in the aging process. A comparison of synaptosome proteins of hippocampus prepared from young-adult (9-week-old) rats with those from aged (30-month-old) rats by two-dimensional fluorescence difference gel electrophoresis revealed 24 spots that were expressed differently among about 1000 spots detected in both young-adult and aged rat samples. Nineteen of these 24 spots were identified by peptide mass fingerprinting. These proteins included chaperone proteins and proteins related to the cytoskeleton, neurotransmission, signal transduction and energy supply. The cytoskeleton-related proteins included actin and T-complex 1, which is thought to play a role in actin folding. Actin was up-regulated but T-complex 1 was down-regulated in aged rat synapses. These results suggest that age-dependent changes of actin filament formation are related to neuronal dysfunction associated with aging.     

Bilateral receptive field neurons in the hindlimb region of the postcentral somatosensory cortex in awake macaque monkeys

Single-neuron activities were recorded in the hindlimb region of the primary somatosensory cortex and part of area 5 in awake Japanese monkeys. A total of 1050 units were isolated from five hemispheres of four animals. Receptive fields (RFs) and submodalities were identified for 90% of isolated neurons in areas 3a and 3b. The percentage decreased as the recoding site moved to the more caudal areas. Deep or skin submodality neurons were dominant in area 3a or area 3b, respectively. Deep submodality neurons increased in more caudal areas and were the majority in areas 2 and 5. These observations were consistent with those in the hand and/or digit or arm and/or trunk region. The identified neurons were classified by their RF positions into four types: the foot, leg, foot and leg, or hindlimb and other body parts type. Among 831 identified neurons, 33 neurons had bilateral RFs, 14 had ipsilateral RFs, and the rest (N=784) had contralateral RFs. The relative incidence of neurons with bilateral or ipsilateral RFs among identified neurons was less than 1% in areas 3a, 3b, and 1, and 16% or 25% in areas 2 or 5, respectively. Within areas 2 and 5, the percentage of neurons with bilateral or ipsilateral RFs was significantly smaller in the foot type (5%) than in other RF types (24-57%). RFs of the foot type were on the sole or single toe but never on multiple toes. These observations contrasted with the previous findings that neurons with bilateral RFs were more frequently seen in the hand and/or digit region and that RFs on multiple digit tips were dominant there. The present study thus demonstrated that neurons with bilateral RFs do exist in the hindlimb region. Similarly to the forelimb region, they were found mostly in areas 2 and 5, the caudalmost areas of the postcentral gyrus and hierarchically higher stages in information processing. The relative paucity of neurons with bilateral RFs on the foot, especially those with RFs on multiple toes, may reflect functional differences between the foot and the hand.     

Coronary arterial lesions in sexually mature non-layers,layers, and roosters

Summary The effects of hereditary hyperlipidemia on coronary artery atherosclerosis were studied in 77 White Leghorn (DeKalb strain) chickens ranging from 4 to 13 months in age. After pubescence, the plasma levels of triglyceride and cholesterol in non-laying hens ranged 2- to 3-fold and 2- to 7-fold higher compared to layers. Serial sectioning revealed that most lesions were found in the proximal portions of both the left and right coronary arteries. Ultrastructurally, lesions in the roosters contained no foam cells, whereas some foam cells and small amounts of stainable lipid were observed in the thickened intima of layers. Half of the non-layers had stenotic lesions characterized by many foam cells, necrotic foci, and heavy stromal lipid deposits. Continuous permeation of excess plasma lipids into the arterial wall appeared to be an important factor in the development of coronary lesions.     

Liver cell membrane antibody detected by protein A and isolated rabbit liver plasma membrane in sera of patients with chronic liver diseases

Using the plasma membrane fraction isolated from rabbit liver (RLPM), we detected non-species specific IgG antibody against liver cell surface membrane in the sera from the patients with chronic liver diseases. The sea were treated with dithiothreitol and iodoacetamide, and absorbed with sufficient amount of actin isolated from rabbit striated muscles. The antibody was detected by incubation of RLPM with the treated and absorbed sera and subsequent determination of IgG bound to RLPM by 125I-staphylococcal protein A. It was found mainly in the patients with autoimmune hepatitis (12 of 28) and liver cirrhosis (eight of 24). It occurred more frequently in HBsAg negative liver cirrhosis than in HBsAg positive forms (six of 13 vs two of 11). The frequency of the antibody was low in chronic hepatitis except autoimmune hepatitis, and primary biliary cirrhosis. Thus the antibody against RLPM was an immunological marker of autoimmune hepatitis and HBsAg negative liver cirrhosis. The occurrence did not correlate with those of anti-smooth muscle antibody, anti-nuclear antibody and anti-mitochondrial antibody. In two cases of autoimmune hepatitis, the antibody against RLPM decreased with clinical improvement induced by corticosteroids.     

Protective effect of recombinant neutrophil elastase inhibitor (R-020) on sepsis-induced organ injury in rat

Severe inflammatory responses after major surgeries, trauma, and infection develop multiple organ dysfunction. In the mechanisms of the pathogenesis of these responses, activated neutrophils are thought to be important in terms of their ability to produce various kinds of proteinases, which can degrade various proteins constructing human tissues. Among their proteinases, neutrophil elastase is the strongest serine proteinase secreted from activated neutrophils. Thus, we examined in this study the inhibitory effect and therapeutic efficacy of newly produced recombinant human Kunitz-type proteinase inhibitor (R-020), which coded the second domain of human urinary trypsin inhibitor. R-020 was effective in significantly improving the survival rate after induction of the rat lethal peritonitis model (cecal ligation and punctureinduced septic shock model). We suggest that various serine proteinases are implicated in the pathogenesis of neutrophil-related multiple organ failure and that recombinant human Kunitz-type proteinase inhibitor might be effective in the treatment of these kinds of organ dysfunction.