Analysis of Responsive Cells in Tolerance by the Oral Administration of Ovalbumin

The induction of immune tolerance is the most common consequence of protein feeding, i.e., “oral tolerance”. In this study we investigated the genetic basis of oral tolerance using various kinds of recombinant and congenic mice, and the cells involved in the development of this phenomenon in mice. The footpad swelling response to ovalbumin (OVA) was inhibited in mice that were orally fed OVA 7 days before sensitization. No effect of strain of mouse was seen in this inhibition. This inhibition could be transferred by Peyer's patch cells. The CD4^-8⁺ T cells were responsible for the inhibition of footpad swelling. The number of CD4⁺ cells from OVA-fed tolerant mice decreased significantly, but CD8⁺ cells did not.

The number of CD4^-8⁺ T cells was increased in Peyer's patches of OVA-fed tolerant mice, and were involved in the development of oral tolerance.     

Antagonistic effects of selective alpha1-adrenoceptor antagonists MDL73005EF and tamsulosin and partial agonists clonidine and tizanidine in rat thoracic aorta and rabbit iliac artery

The antagonistic effects of MDL73005EF and tamsulosin and partial agonists clonidine and tizanidine at rat thoracic aorta and rabbit iliac artery alpha1-adrenoceptors were investigated in this study. Selective alpha1-adrenoceptor antagonists MDL73005EF and tamsulosin dose-dependently shifted the concentration-response curves for noradrenaline to the right. Schild plots of the results obtained from the inhibition by MDL73005EF (pA2 8.30 +/- 0.04) and tamsulosin (pA2 10.51 +/- 0.06) of noradrenaline yielded a straight line with a slope of unity in rat thoracic aorta. The slopes of Schild plots obtained from the inhibition by MDL73005EF and tamsulosin of noradrenaline were significantly different from unity in rabbit iliac artery. Schild plots of the results obtained from the inhibition by clonidine and tizanidine of noradrenaline yielded a straight line with a slope of unity in rat thoracic aorta (pA2 7.08 +/- 0.04 and 7.32 +/- 0.04, respectively). These results suggest that alpha1D-adrenoceptors play a significant role in the alpha1-adrenoceptor-agonist-induced contraction of rat thoracic aorta and rabbit iliac artery, and that clonidine and tizanidine interact with the alpha1D-adrenoceptor subtype as competitive antagonists in rat thoracic aorta.     

Similarities between the relaxations induced by vasoactive intestinal peptide and by stimulation of the non-adrenergic non-cholinergic neurons in the rat stomach

Summary The characteristics of the non-adrenergic, noncholinergic inhibitory response of the rat stomach fundus to transmural nerve stimulation were compared with the relaxation induced by vasoactive intestinal polypeptide (VIP). Treatment with -chymotrypsin (5 U/ml) or VIP antiserum (1:200) significantly reduced the relaxation induced by transmural nerve stimulation at 30 Hz, indicating that the possible transmitter in the non-adrenergic, non-cholinergic nerves is a peptide and may be VIP or a closely related peptide. VIP was able to relax, fully and dose-dependently, the stomach fundus that had previously been constricted by treatment with 10^–6 M serotonin, and the IC₅₀ value for VIP was 2.4 × 10^–9 M. VIP elevated levels of cyclic AMP in a dose-dependent manner and the EC₅₀ value was 2.8 × 10^–9 M in the presence of 10^–6 M atropine and 10^–6 M guanethidine. The stomach fundus was relaxed by transmural nerve stimulation (30 Hz, 50 mA) and transmural nerve stimulation also caused production of cyclic AMP in the rat stomach in the presence of atropine and guanethidine. The basal level of cyclic AMP in the stomach was 8.7 ± 0.26 pmole/mg protein. When transmural nerve stimulation was applied for 5 min, the contraction of the stomach, induced by 10^–6 M serotonin, was inhibited by 54% in the presence of atropine and guanethidine and the level of cyclic AMP was increased to 13.0 ± 0.73 pmol/mg protein. Apamin inhibited the transmural nerve stimulation-induced relaxation and shifted the dose-response curve for VIP to the right. These results suggest that one of the putative neurotransmitter from non-adrenergic, non-cholinergic nerves in the rat stomach is VIP and that VIP-induced relaxation may be mediated by the production of cyclic AMP and by the opening of apamin-sensitive K⁺-channels.Send offprint requests to K. Kamata at the above address     

A new closed-system using partially frozen injectate for thermodilution cardiac output determinations

The FI (partially frozen injectate) system, a new closed-system devised by the authors for thermodilution cardiac output determinations, has two major features: 1) it needs no ice-filled receptacle to keep injectate cold because it uses partially frozen injectate, and 2) it can go without monitoring the injectate temperatures during the whole process of cardiac output determinations. The author evaluated the accuracy and reproducibility of cardiac output determinations with the FI system in 10 critically ill patients, as compared with another closed-system (which is commercially available) and the standard open method. The injectate temperatures in the FI system were also measured in vitro. The mean injectate temperature in the FI system was 0.71 ± 0.26°C and 80% of the injectate temperatures were lower than 1.0°C. Even when no monitoring of injectate temperatures was made, the predicated error in the calculated cardiac output resulted as low as 2% with the FI system. The mean cardiac output values were not statistically different between the FI system and the other two systems.(Maruta H, Usuda Y, Okutsu Y et al.: A new closed-system using partially frozen injectate for thermodilution cardiac output determinations. J Anesth 3: 35–39, 1989)     

Effects of calcitonin gene-related peptide on canine cerebral artery strips and the in-vivo vertebral blood flow in dogs

Summary The effects of calcitonin gene-related peptide (CGRP) on canine cerebral arteries and on vertebral blood flow were investigated in-vivo and in-vitro and the findings compared with the effects of vasoactive intestinal peptide (VIP) and substance P. Administration of CGRP into the vertebral artery caused a dose-dependent and long-lasting increase in blood flow. The in-vivo vasodilatory effects of substance P and VIP were short-lasting. CGRP (0.1 to 100 nmol/l) elicited a concentration-dependent relaxation of the isolated middle cerebral and basilar arteries when the tissues were precontracted by exposure to prostaglandin F₂ (PGF₂). This effect was not antagonized by propranolol, atropine, tetrodotoxin, (N-Ac-Tyr¹, D-Phe²)-growth hormone-releasing factor(1–29)-NH₂ or (D-Pro², D-Trp^7,9) substance P. CGRP also reduced concentration-dependently the contraction of cerebral arteries induced by KCl or 9,11-epithio-11,12-metano-thromboxane A₂ (STXA₂). Mechanical removal of the endothelium did not abolish the vasodilatory response to CGRP. In PGF₂-contracted canine cerebral arteries, VIP (0.1 to 100 nmol/l) was less potent a vasodilator than CGRP. At low concentrations (0.01 to 1 nmol/l) substance P elicited a rapid and short-lasting relaxation, and in the absence of endothelium this relaxation disappeared. These findings are clear evidence that CGRP modulates vascular tone.     

Immunological analysis of plasminogen activators from cultured human cancer cells

Summary Immunological similarities or differences between urokinase and plasminogen activators from 9 lines of cultured human caner cells with varying degrees of fibrinolytic activity were examined with antibodies against human urokinase.The antibodies completely inhibited the fibrinolytic activity of 4 lines of gastric cancer, 2 lines of lung cancer, 1 line of urinary bladder cancer and 1 line of renal cancer, indicating that the plasminogen activators from these cell lines were immunologically identical to urokinase. In 5 out of these cell lines, immunological identity was also confirmed by double diffusion analysis.The plasminogen activator from 1 line of lung cancer was found to be immunologically dissimilar to urokinase by a neutralization experiment and double diffusion analysis.These findings indicate that there are at least two immunologically distinguishable forms of plasminogen activators from human cancer cells.     

Induction and activation of the aryl hydrocarbon receptor by IL-4 in B cells

It is widely known that IL-4 and IL-13 act on various kinds of cells, including B cells, resulting in enhancement of proliferation, class switching to IgE and expression of several surface proteins. These functions are important for the recognition of the various antigens in B cells and are known to be involved in the pathogenesis of allergic diseases. However, it has not been known whether IL-4/IL-13 is involved in the metabolism of various kinds of xenobiotics including 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), and it remains undetermined whether TCDD, an environmental pollutant, influences IgE production in B cells, exaggerating allergic reactions. We identified IL-4- or IL-13-inducible genes in a human Burkitt lymphoma cell line, DND-39, using microarray technology, in which the AHR gene was included. The AHR gene product, the aryl hydrocarbon receptor (AhR), was induced by IL-4 in both mouse and human B cells in a STAT6-dependent manner. IL-4 alone had the ability to translocate the induced AhR to the nuclei. TCDD, a ligand for AhR, rapidly degraded the induced AhR by the proteasomal pathway, although IL-4-activated AhR sustained its expression. AhR activated by IL-4 caused expression of a xenobiotic-metabolizing gene, CYP1A1, and TCDD synergistically acted on the induction of this gene by IL-4. However, the induction of AhR had no effect on IgE synthesis or CD23 expression. These results indicate that the metabolism of xenobiotics would be a novel biological function of IL-4 and IL-13 in B cells, whereas TCDD is not involved in IgE synthesis in B cells.     

Electrophysiological comparison between patients with Binswanger's encephalopathy and Alzheimer's disease

Short-latency somatosensory (SSEPs), brainstem auditory evoked potentials (BAEPs) and event-related potentials (ERPs) were studied in 7 patients with Binswanger's encephalopathy, 12 patients with Alzheimer's disease and 17 normal subjects. Patients with Binswanger's encephalopathy showed significantly prolonged central conduction time (CCT) and P300 latency, and prolonged tendency of I-V IPL compared to those of normal subjects. In particular, CCT showed significant prolongation compared to that of patients with Alzheimer's disease. In patients with Alzheimer's disease, I-V IPL and P300 latency were significantly prolonged compared to those of normals although there was no significant difference in CCT between Alzheimer's disease and normal subjects. These results indicate some difference between Binswanger's encephalopathy and Alzheimer's disease from the electrophysiological aspects although both of these entities are characterized by progressive mental deterioration.     

Ras homolog gene family H (RhoH) deficiency induces psoriasis-like chronic dermatitis by promoting TH17 cell polarization

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FAMILIAL NEPHROPATHY ASSOCIATED WITH HEPATIC TYPE OF GLYCOGEN STORAGE DISEASE

The female patient was diagnosed as having Von Gierke's disease at 14 years of age, based on clinical manifestations, laboratory examination and liver biopsy. At 19 years of age she had uremia and died from its deterioration at 24 years of age. The parents were consanguineous, and a 27-year-old sister is presently hospitalized for renal Insufficiency with hepatomegaly. On autopsy, the patient's kidneys were highly contracted and contained a number of small cysts, mainly in the medulla. Histological examination indicated periglomerular fibrosis, glomerular hyalinization, tubular atrophy or cystic dilatation and intersitial fibrosis with round cell infiltration. These findings correspond to Fanconi's familial juvenile nephronophthlsis, except for age. The liver was markedly enlarged and Indicated severe glycogen deposits, but the kidney did not contain glycogen deposits. It can, therefore, be presumed that the renal lesions were not a secondary consequence of long-term glycogen deposits but that renal and hepatic lesions were associated with each other.