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Notes: Summary Exercise-induced anaphylaxis (EIA) is a form of physical urticaria that is induced by exercise. A 16-year-old Japanese boy had a 4-year history of recurrent wealing and dyspnoea after physical exercise such as jogging, playing handball or riding a bicycle in winter. The episodes were not associated with ingestion of foods including wheat or soya bean. A provocation test, with 15 min of exercise and 2 min of cold stimulation immediately before or immediately after the exercise, elicited a weal that was localized to the test area. A challenge test with ingestion of boiled soya beans and exercise did not elicit a weal. Therefore, in this case, cold exposure, but not food ingestion, was essential for inducing EIA. Cold-dependent EIA is different from cold urticaria, food-dependent EIA, cholinergic urticaria and cold-induced cholinergic urticaria, and may be a distinct entity.

Notes: In our previous study, apparent reduction of glucocorticoid receptor (GR) mRNA was seen in the hippocampus and the hypothalamic paraventricular nucleus (PVN) during repeated immobilization (IMO) stress, but not following starvation. Our laboratory has also shown that the sp1 activates, whereas tumour suppressor p53 represses the promoter activity of GR gene. In an attempt to reveal the possibility that transcription factors such as sp1 and/or p53 are involved in the regulation of GR mRNA expression in the hippocampus and in the PVN in vivo, we examined the expression of GR mRNA, p53 mRNA, and sp1 mRNA in the hippocampus and in the PVN during repeated IMO and following starvation. In addition, the expression of these mRNAs was examined in the anterior pituitary, another GR-rich area. GR mRNA in all subfields of the hippocampus was robustly decreased, while GR mRNA in the anterior pituitary was increased, 24 h following 4 × IMO (2 h daily, for 4 consecutive days) and immediately after 5 × IMO. GR mRNA in the PVN was significantly decreased immediately after 5 × IMO, but not at 24 h after 4 × IMO. Conversely, p53 mRNA in the PVN and hippocampus was increased, whereas p53 mRNA in the anterior pituitary was decreased, 24 h following 4 × IMO and immediately after 5 × IMO. Sp1 mRNA was unchanged in all areas examined following repeated IMO. Following 4 days of starvation, neither GR mRNA, p53 mRNA nor sp1 mRNA showed any changes in the PVN and the hippocampus, except there was a minor decrease in GR mRNA in CA1-2. In the anterior pituitary, 4 days of starvation induced a minor, but significant increase in GR mRNA, whereas it decreased p53 mRNA. Overall, regression analyses revealed a negative correlation between GR mRNA levels and p53 mRNA levels in CA1-2 and dentate gyrus of the hippocampus and in the anterior pituitary. GR mRNA in the PVN also showed a tendency towards the negative correlation with p53 mRNA levels. The results raise the possibility that p53 negatively regulates GR mRNA expression in the PVN, the hippocampus and the anterior pituitary during repeated immobilization stress.

Notes: During starvation, counterregulatory responses to loss of food (i.e. responses that lead to an increase in appetite) occur in the central nervous system (CNS). This study was designed to examine whether middle-aged rats show greater or smaller behavioural, peripheral and central hormonal responses during starvation compared to young rats. In experiment 1, refeeding following 4 days of starvation was measured in both middle-aged (72-week-old) and young (9-week-old) rats. The level of refeeding was similar to each prestarved level until 3 days after the end of starvation in both groups. From the 4th day, the level of refeeding in young rats increased and reached beyond the prestarved level, whereas refeeding in middle-aged rats remained similar to the prestarved level. Thus, overall refeeding throughout 7 days was greater in young rats than in middle-aged rats. In experiment 2, middle-aged and young rats were starved for 4 days and were killed in the morning. Middle-aged rats showed a smaller plasma corticosterone response than that of young rats. The magnitude of decreases in plasma glucose, insulin and leptin was similar in both groups. In the arcuate nucleus, the starvation-induced increase in neuropeptide Y (NPY) mRNA and the decrease in proopiomelanocortin (POMC) mRNA were smaller in middle-aged rats than in young rats. In contrast, the starvation-induced decrease in corticotrophin-releasing hormone (CRH) mRNA in the hypothalamic paraventricular nucleus was greater in middle-aged rats than young rats. The magnitude of decrease in type-2 CRH receptor mRNA in the ventromedial hypothalamus was similar in both groups. The results indicate that (a) ageing impaired refeeding response (b), middle-aged rats showed the same directional neuropeptide mRNA responses as seen in young rats during starvation and (c) the magnitude of these counterregulatory responses in the CNS in middle-aged versus young rats was not uniform, but rather was site-specific or neuropeptide-specific. This study suggests the importance of NPY and POMC responsiveness in the arcuate nucleus in the age-related differences resulting from starvation-induced refeeding.

Notes: Regulation of acute-phase serum amyloid A (A-SAA) synthesis by proinflammatory cytokines and steroid hormones in human aortic smooth muscle cells (HASMCs) is distinct from that in HepG2 cells. To study the cis- and trans-activating promoter element involved in the SAA1 gene expression by HASMCs and HepG2 cells, we constructed plasmid vectors for luciferase reporter gene assay with varying lengths of SAA1 upstream regulatory region (up to 1431 bp), and examined their response to proinflammatory cytokines and/or steroid hormones. The corresponding vectors with the SAA4 upstream regulatory region served as controls. The presence of proposed transcriptional regulatory factors binding to these regions was confirmed immunohistochemically.The sequences of 1478 and 1836 bp of the SAA1 and SAA4 5′-flanking regions were determined, respectively. SAA1 promoter transcription in cultured HASMCs was upregulated not by proinflammatory cytokines, but rather by glucocorticoids. This differed from HepG2 cells, in which SAA1 promoter transcription was upregulated synergistically by proinflammatory cytokines and glucocorticoids. The promoter activity of a series of truncated SAA1 promoter constructs measured using the reporter gene assay showed that the 5′-region from −252 to −175, containing a consensus site for CCAAT/enhancer binding proteins α,β (C/EBPα,β), was essential for SAA1 induction in HASMCs. In HepG2 cells, the 5′-region from −119 to −79, containing a nuclear factor kappa-B (NFκB) consensus sequence, was essential for the induction. The functional significance of the C/EBP site as indicated by the immunohistochemical result was that in HASMCs anti-C/EBPβ reactivity was shifted from the cytoplasm to the nuclei.We have, therefore, demonstrated that the region containing the C/EBPα,β consensus binding site between the bases −252 and −175 is important for the glucocorticoid-induced SAA1 gene expression in HASMCs but not in HepG2 cells.

Notes: Although the SAA1 and SAA2 protein isoforms (A-SAA) of the serum amyloid A (SAA) family of acute phase reactants have been found in a number of extrahepatic tissues; the site of synthesis of extrahepatic SAA remains to be clarified. To investigate site(s) of synthesis of the SAA protein localized to atherosclerotic plaque, expression of the SAA1 and SAA2 genes by cultured human aortic smooth muscle cells (HASMC) was investigated. A-SAA protein isoforms were detectable by immunoblot analysis in the culture medium of HASMC. Both A-SAA and C-SAA (SAA4) mRNA isoforms were constitutively expressed by HASMC, but not, however, by the human umbilical vein endothelial cells. Expression of A-SAA mRNA by HASMC was upregulated by corticoid hormones including dexamethasone (Dex), corticosterone, hydrocortisone, and aldosterone, but not by the cytokines interleukin (IL)-1, IL-6, and tumour necrosis factor (TNF)-α alone. Dex stimulation of A-SAA mRNA was time and dose dependent from 6 to 48 h. The threshold concentration for upregulation of A-SAA mRNA in HASMC by Dex was between 0.1 and 1 nm. IL-1, known to upregulate extrahepatic A-SAA gene expression in other cell systems only slightly, if at all, upregulated Dex-induced A-SAA expression by HASMC. Thus, it is possible that some of the A-SAA protein in the vascular wall (atherosclerotic plaques) can originate from smooth muscle cells. In consideration of recent reports that A-SAA modulates the inflammatory process and lipid synthesis, A-SAA can potentially serve as a physiological regulator of smooth muscle cell homeostasis within that, in a disease state, participates in the formation of atherosclerotic plaques.

Notes: 1. The antiarrhythmic properties of 5–(3-tert-butylarnino-2-hydroxy)propoxy-3,4-dihydrocarbostyril hydrochloride (OPC-1085) were compared with those of propranolol and pindolol using various kinds of preparations for experimental arrhythmia in dogs.2. Although OPC-1085 was the most potent drug to antagonize adrenaline-induced arrhythmia in animals anaesthetized with either pentobarbitone sodium or halothane, it was scarcely effective on ouabain-induced arrhythmia in pentobarbitone sodium anaesthetized animals.3. When these compounds were administered intravenously to conscious dogs 24 h after two-stage ligation of the anterior descending artery, ectopic ventricular beats of coronary ligation-induced arrhythmia were reduced while regular sinus beats were simultaneously increased.4. OPC-1085 was very effective on aconitine-induced arrhythmia in dogs anaesthetized with pentobarbitone sodium. The effective dose was similar to that of propranolol but about fifteen times less than that of pindolol.5. It is concluded that different potencies among these β-adrenoreceptor antagonists against various kinds of experimental arrhythmias cannot be simply deduced from any one of the following properties; β-adrenoreceptor antagonism, intrinsic myocardial stimulation, local anaesthetic and so-called quinidine-like effects.

Notes: 1. The effects of glucagon on the secretion of pancreatic juice were investigated using blood-perfused canine pancreas preparations.2. Intravenous administration of glucagon (3–30 μg/kg) to the donor dog elicited a dose-dependent increase in pancreatic secretion. Intra-arterial administration of glucagon (10–100 μg) into the perfused pancreas also elicited increased secretion.3. There were slight increases in amylase concentration of the pancreatic juice with the largest doses of glucagon given by either route.4. Glucagon-induced secretion was not modified by treatment with phentolamine, propranolol, atropine, guanethidine, tetrodotoxin, haloperidol, prostaglandin F2a or calcitonin.5. The results suggest that glucagon acts directly on the exocrine cells of the canine pancreas.

Notes: 1. Effects of calcitonin on dopamine-, secretin- and pancreozymin-induced pancreatic secretion were investigated in the isolated blood-perfused canine pancreas.2. The volume of pancreatic secretion induced by pancreozymin given intra-arterially (i.a.) was decreased by an i.a. infusion of 1 u/min of calcitonin, but that induced by dopamine or secretin given i.a. was not affected by calcitonin treatment.3. Amylase concentration in pancreatic juice either in spontaneous secretion in the resting state or in that of stimulated secretion by pancreozymin was decreased approximately 30% by calcitonin treatment, but amylase concentration in pancreatic juice induced by dopamine or secretin was not affected by calcitonin treatment.4. Calcitonin had no effect on bicarbonate concentration in pancreatic juice stimulated by these secretagogues.5. Calcium concentration in pancreatic juice in the resting state was reduced about 36% by calcitonin treatment. Calcitonin caused a decrease in a calcium concentration in the pancreozymin-induced secretion, but did not cause any change in the dopamine- or secretin-induced one.6. These results suggest that calcitonin may affect the secretory mechanism of the acinar cells but not that of the ductular cells, and that the acinar cells are active even in the resting state.

Notes: The purpose of the present study was to elucidate the effects of unilateral masseter muscle pain on the jaw-jerk reflex. The latency and peak-to-peak amplitude of bilateral electromyographic activity recorded at the masseter muscles during the jaw-jerk reflex were measured in 18 patients with craniomandibular dysfunction (CMD) with strictly unilateral masseter pain or tenderness and 10 control subjects using a computerized recording and analysis system. The reflex was elicited, at the mandibular rest position, by tapping the centre of the chin downwards with a reflex hammer incorporating a microswitch that triggered the sweep of the recording apparatus upon contact with the chin. In the CMD group, the jaw-jerk latency on the affected side (6·89±0·98 ms) was significantly shorter (P〈0·01) than that on the unaffected side (7·59±0·92 ms). In the control group, there was no difference between the jaw-jerk latencies on the right (7·06±0·64 ms) and the left (7·08±0·65 ms) sides. The range of side asymmetry for jaw-jerk latencies in the CMD group was greater than that in the control group. In six patients, the latency difference exceeded 1 ms. The asymmetry of latency of the jaw-jerk reflex was thought to be due to facilitation on the side with masseter pain or tenderness. This facilitation on the ipsilateral side might be produced by enhanced gamma drive induced by sustained nociceptive stimulation. Such effects may be related with clinically derived concepts regarding such muscle dysfunction as myospastic activity or trigger points.