Newly appreciated roles for basophils in allergy and protective immunity.

Basophils are evolutionarily conserved in many animal species, in spite of the fact that they account for <1% of peripheral blood leukocyte. This suggests that basophils have an indispensable and nonredundant role in vivo, even though they show some phenotypic similarity with tissue-resident mast cells. However, their functional significance remained uncertain long after Paul Ehrlich discovered them as blood-circulating cells with basophilic granules more than 130 years ago. The study of basophils has been far behind that of mast cells, owing to the rarity of basophils and the paucity of tools for their detection and functional analysis. Recent development of novel analytical tools, including basophil-depleting antibodies and genetically engineered mice deficient only in basophils, has greatly advanced basophil research and illuminated previously unrecognized roles of basophils. We now appreciate that basophils and mast cells play distinct roles in immune responses. Basophils have crucial roles in the development of acute and chronic allergic responses, the protective immunity against ecto- and endoparasites, and the regulation of acquired immunity, including the augmentation of humoral memory responses and the initiation of Th2 responses. Thus, basophils are no longer the neglected minority and are key players in the immune system.

Downfolding of the epiglottis induced by the laryngeal mask airway in children: a comparison between two insertion techniques.

BACKGROUND: The purpose of this study was to compare the incidence of the downfolding of the epiglottis in children during insertion of the laryngeal mask airway (LMATM) using the standard technique and an alternative technique with the cuff partially inflated. METHODS: Eighty paediatric patients were randomized into two groups and were anaesthetized using the LMA inserted with one of the two techniques. RESULTS: There was no difference in the successful rate of insertion, fibreoptic findings and the lowest intraoperative SpO2 between the two groups. CONCLUSIONS: The partially inflated cuff insertion technique does not increase the incidence of the downfolding of the epiglottis in children and would be an acceptable alternative to the standard technique.

Ventricular parasystolic couplets originating in the pathway between the ventricle and the parasystolic pacemaker: mechanism of "irregular" parasystole.

This article explains the mechanism of "irregular" parasystole. Two theories have been suggested: "electrotonic modulation" and "type I second degree entrance block." This study attempts to clarify the mechanism of irregular parasystole in cases of true ventricular parasystole associated with ventricular parasystolic couplets. Cases associated with ventricular parasystolic couplets were selected from 37 clinical cases of true ventricular parasystole in which one or more pure parasystolic cycles with no intervening nonectopic QRS complexes were found. Of the 37 cases of true ventricular parasystole, ventricular parasystolic couplets were found in 4 cases. In none of the other 33 cases, ventricular parasystolic couplets were found. In all the cases coexisting with ventricular parasystolic couplets, the latter ectopic QRS complex of the couplet failed to reset the parasystolic rhythm. The above findings suggest that the latter ectopic QRS complex of the parasystolic couplet originated not in the parasystolic pacemaker but in the pathway between the ventricle and the parasystolic pacemaker. It seems that when a sinus impulse fell late in the parasystolic cycle, it passed through the site of second degree entrance block and that the parasystolic couplets originated from the reentrant pathway between the ventricle and the pacemaker. This strengthens our previous suggestion that the mechanism of irregular parasystole is governed by "type I second degree entrance block" and not by "electrotonic modulation."

Repetitive supernormal conduction in the right bundle branch in high degree bilateral bundle branch block.

Electrocardiograms were taken from a 67-year-old woman with high-degree atrioventricular block in which ventricular escape beats of right bundle branch block pattern occurred, accompanying occasional ventricular capture beats. Only when a sinus P wave occurred 0.60 s after the preceding escape beat, it was followed by a capture beat of left bundle branch block pattern with the RP interval of 0.60 s and the PR interval of 0.19 s. Similar left bundle branch block with left axis deviation pattern had been shown in the electrocardiogram taken 2 years before. Such RP and PR intervals in capture beats were invariable. These suggest that capture beats occurred as a result of supernormal conduction in the right bundle branch, which denies the possibility of ventricular extrasystoles. Such capture beats with the above RP and PR intervals were observed repeatedly.

Apparent bradycardia-dependent right bundle branch block associated with atrial fibrillation: concealed electrotonic conduction as a possible mechanism.

A 79-year-old woman with atrial fibrillation was reported in whom apparent bradycardia-dependent right bundle branch block was suggested. When a conducted supraventricular impulse occurred within a critical period after the preceding conducted impulse, the impulse was blocked in the right bundle branch except when it fell in the supernormal period of the right bundle branch. When the conducted impulse occurred between the critical period and another longer period, it was conducted without bundle branch block. When the impulse occurred beyond that longer period, it was usually blocked in the bundle branch again. However, when the impulse occurred beyond a still longer period, it was conducted without bundle branch block again. These findings suggest that when impulses fell in the right bundle branch shortly after the preceding conducted impulses, they were blocked in both bundle branches; however, it seemed that concealed electrotonic conduction of the blocked impulses affected conduction of the subsequent impulses.

Development of a new matrix based on a silicone ladder polymer for ion-sensing membranes.

A silicone ladder-type polymer was successfully utilized for a matrix of an ion sensing membrane to fabricate an ion-sensitive field-effect transistor. An ion sensing membrane was readily fabricated by mixing a silicone ladder-type oligomer with a quaternary ammonium salt, casting onto the gate of the field-effect transistor, and polymerizing with heating. Since no acid catalysts were needed to prepare the ion sensing membrane, it was possible to keep the quaternary ammonium salt in the matrix without decomposition. The ion-sensitive field-effect transistor based on the silicone ladder-type polymer and the quaternary ammonium salt showed a linear response with a slope of -58.1 mV decade(-1) very close to the theoretical Nernstian response over an NO3- range between 3.0 x 10(-6) and 1.0 x 10(-1) M. The time required to reach 90% total response was within 5 s, when the NO3- concentration was changed from 1.0 x 10(-3) to 3.0 x 10(-3) M. The newly fabricated ion-sensitive field-effect transistors have kept their original sensitivity for more than half a year.

Highly selective iodide-sensing silicone ladder polymer membranes containing a porphyrin and a quaternary ammonium salt.

It has been demonstrated that a glass-like silicone ladder-type polymer permits one to homogeneously incorporate high amounts of ionophores into the covalently-bonded double chain structure. Furthermore, by making use of this feature, we have successfully fabricated an iodide ion-sensitive field-effect transistor based on two kinds of ionophores and silicone ladder polymer matrix. As ionophores, 5,10,15,20-tetraphenyl-21H,23H-porphyrin and dimethyloctadecyl-3-trimethoxylsilylpropylammonium chloride were homogeneously incorporated into the matrix. The ion-sensitive field-effect transistor showed a linear potential response ranging in the I- concentration between 1.0 x 10(-5) and 1.0 x 10(-1) M. The selectivity coefficients for I- towards interferences of ClO4- and NO3- were estimated to be Kpot(I-,ClO4-) approximately 6.2 x 10(-4) and Kpot(I-,No3-) approximately 4.9 x 10(-4). The matrix has proved to be so stable that the selectivity coefficients have not been altered over six months.

Sinus escape-capture bigeminy and sinus extrasystolic bigeminy.

Blocking conduction between the sinus node and the atria (SA block) can be responsible for symptomatic rhythm problems. However, in atrial escape-capture bigeminy with SA block, when atrial escape P waves originate in a site within or close to the sinus node, the diagnosis of SA block is not easy. Electrocardiograms were selected from 7 people with atrial bigeminy because (1) all atrial deflections (P waves) were almost the same in shape and in length of PR intervals, (2) comparatively long PP intervals alternated with comparatively short PP intervals, and (3) occasionally the atrial bigeminy changed to normal regular sinus rhythm in which 2 or more sinus P waves were found in succession. An attempt is made to clarify the mechanism for these cases. When regular sinus rhythm changed to bigeminal rhythm, the long PP interval introduced the bigeminy in 3 cases, indicating the presence of "sinus" escape-capture bigeminy; whereas the short PP interval introduced the bigeminy in the other 4 cases, indicating the presence of "sinus" extrasystolic bigeminy. In cases of sinus escape-capture bigeminy associated with SA block, the cases may occasionally be diagnosed wrongly as ordinary sinus arrhythmia not associated with SA block. Therefore, it seems that sinus escape-capture bigeminy is not so rare as is generally believed. Patients with SA block often require implantation of the artificial pacemaker. Thus, the authors believe that differentiation of sinus escape-capture bigeminy from other forms of "sinus" bigeminy is clinically important.

Tachycardia-dependent right bundle-branch block with supernormal conduction.

This paper reports the case of a 76-year-old man in whom atrial flutter with varying atrioventricular block and intermittent right bundle-branch block was found. This is the first report on tachycardia-dependent right bundle-branch block associated with supernormal conduction in a case of atrial flutter. When an impulse is conducted to the ventricles beyond 0.72 s after a QRS complex of right bundle-branch block configuration, the impulse falls after the abnormally long effective refractor period of the right bundle branch and passes through the right bundle branch. When the conducted impulse occurs within 0.72 s after a QRS complex of right bundle-branch block configuration, the impulse usually falls in the refractory period and is blocked in the right bundle branch; however, only when the impulse occurs 0.48 or 0.49 s after that does it fall in the supernormal period and passes through the right bundle branch. The findings in the present report strengthen our previous suggestion that the presence of supernormal conduction plays an important role in the initiation of reentrant ventricular tachycardia.

An experience for ELISA for desmoglein 1, suggesting a possible diagnostic help to determine the initial therapy for pemphigus foliaceus.

Pemphigus foliaceus (PF) is an autoimmune skin disease in which loss of adhesion between keratinocytes (i.e., acantholysis) in the granular cell layers appears to be mediated by the binding of autoantibodies against desmoglein (Dsg) 1. Although it has been suggested that the activity of the disease is rather correlated with the titer of the antibody, there are still no precise studies on the relationships between the disease activity and the titers of autoantibody against Dsg1 by using ELISA. In this study, we performed ELISA using recombinant Dsg1 (rDsg1) as antigen on 8 patients with pemphigus foliaceus in order to examine the reliability of this test for monitoring disease severity. The resultant index values of ELISA, which were defined by the formula: (OD of tested serum - OD of negative control)/(OD of positive control - OD of negative control) X 100, ranged from 16 to 264 compared with 6.41 of cutoff index value for normal sera. A patient with an index value of 213 had severe widespread erosions with erythema and required pulse therapy of methylpredonisolone (1,000 mg/day for 3 days). A patient with an index value of 111 had a moderate severity and was successfully treated with an initial dose of 30 mg/day (0.64 mg/kg) of predonisolone. The mildest patient with an index value of 16 was controlled with only topical application of 0.05% betamethasone ointment twice a day. These results suggest that ELISA index values for rDsg1 will provide a promising tool for monitoring the disease severity and for determining the initial therapy for pemphigus foliaceus.

Metabolism substrate with negative myocardial uptake of iodine-123-BMIPP.

UNLABELLED: Iodine-123-BMIPP is an iodinated methyl-branched-chain fatty acid. Low uptake of BMIPP relative to thallium or other perfusion tracer indicates metabolically damaged but viable myocardium (for example, ischemic but viable myocardium). In some cases, however, negative myocardial uptake of BMIPP is observed. The main purposes of this study were to assess the frequency of such BMIPP findings and to clarify metabolism of such cases by using PET. METHODS: Among the 1258 patients who underwent BMIPP scintigraphy, 11 patients (0.9%) showed negative myocardial uptake of BMIPP. Under fasting condition, PET using [11C]palmitate, 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and [11C]acetate was performed in nine of these 11 patients. RESULTS: Global myocardial uptake of [11C]palmitate, expressed as the standardized uptake value, was significantly lower in the patients than in control (3.62 +/- 0.44 versus 5.49 +/- 1.62; p < 0.01). However, the early phase clearance rate of [11C]palmitate and oxidative metabolism was not significantly different. In the fasting state, PET studies showed increased FDG accumulation in seven of nine patients (high group) and decreased accumulation in two patients (low group). In the high group patients, glucose metabolism in the fasting state was similar to that in the normal volunteers after glucose loading (Kcomplex: 0.050 +/- 0.016 versus 0.038 +/- 0.015; p = ns). However, low glucose metabolism was noted in the low group patients (Kcomplex: 0.007 and 0.005). CONCLUSION: Negative myocardial uptake of BMIPP is occasionally, but not often, observed. Global uptake of [11C]palmitate was decreased in these patient. The majority of these patients showed "metabolic switching" from normal free fatty acid metabolism to abnormally enhanced glucose metabolism in the fasting state. However, some patients showed decreases in both exogenous glucose utilization and free fatty acid uptake in the fasting state.

[Polysaccharides in fungi. XXXIII. Hypoglycemic activity of an acidic polysaccharide (AC) from Tremella fuciformis].

Glucuronoxylomannan (AC) from the fruiting bodies of Tremella fuciformis exhibited a significant dose-dependent hypoglycemic activity in normal mice and also showed a significant activity in streptozotocin-induced diabetic mice, by intraperitoneal (i.p.) administration. The activities of AC-derivatives such as a product of AC which side chains had been removed were lower than that of native AC. AC raised the plasma insulin level in normal mice. Administration of AC to normal mice significantly increased the activities of hepatic hexokinase and glucose-6-phosphatase dehydrogenase, but it decreased that of hepatic glucose-6-phosphatase. Furthermore, AC reduced the glycogen content in the liver, increased the total lipid in epididymal adipose tissue, and lowered the plasma cholesterol level. The foregoing results indicated that the hypoglycemic activity of AC in normal mice was at least responsible for the increase of insulin secretion and for the acceleration of glucose metabolism. Single oral administration at a dose of 50-300 mg/kg of AC did not affect the plasma glucose level in normal mice, but continuous oral administrations of the AC solution (0.75 g/l) instead of water for a long time was found to be effective on the plasma glucose level in both experiments of the mice injected once i.p. with streptozotocin (170 mg/kg) at 0 d of AC administration and streptozotocin-induced diabetic mice.

Endothelin enhances delayed potassium current via phospholipase C in guinea pig ventricular myocytes.

The effects of endothelin, a novel vasoconstrictive peptide, on the delayed rectifier K+ current (IK) were examined in single dialyzed cells from guinea pig ventricles. Either big endothelin or endothelin-1 enhanced IK at a dissociation constant of 2 nM with L-type Ca2+ current being unaffected. Under intracellular perfusion with pCa 7.6 solution, 3 nM big endothelin increased IK by 55 +/- 38.5%. Either pretreatment with 10 microM 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H 7) or a low Ca2+ [10 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) and minus CaCl2] internal solution diminished the enhancement. Preceding stimulation of protein kinase C (PKC) by 10-20 nM 12-O-tetradecanoylphorbol-13-acetate also reduced the degree of enhancement. When Na+ was eliminated from the solutions, endothelin increased IK distinctively in cells internally dialyzed with a low Ca2+ solution. This enhancement was not abolished by either pretreatment with H 7 or by removal of Ca2+ from the external perfusate but by increasing the internal EGTA concentration to 40 mM. Preincubation with ryanodine or internal perfusion with heparin also reduced the IK enhancement under Na(+)-free conditions. Intracellular application of 200 microM guanosine 5'-O-(3-thiotriphosphate) effectively attenuated the effect of endothelin. It is concluded that endothelin enhances IK via phospholipase C-mediated PKC activation and intracellular Ca2+ mobilization. GTP-binding protein is involved in these reactions.

Attenuation of gastric effects of famotidine by preoperative administration of intravenous fluids.

Effects of preoperative administration of intravenous crystalloids on the gastric effects of famotidine were studied in 89 patients scheduled for elective surgery in the afternoon. Patients were randomly assigned to one of six groups. Groups P1, P2, and P3 received 2.0 mL of intramuscular saline (placebo) and groups F1, F2, and F3 received 20 mg of intramuscular famotidine 1 h before anesthesia. All patients fasted for 14-18 h before surgery. No fluid was administered to groups P1 and F1 preoperatively, whereas 500 mL of intravenous fluid was given to the other groups over a period of 4-5 h before anesthesia: a maintenance fluid with 10% glucose to groups P2 and F2, and lactated Ringer's solution without glucose to groups P3 and F3. After anesthetic induction, the stomach was aspirated using a nasogastric tube and volume and pH of the contents were measured. The gastric volume was significantly less in F2 (4.2 +/- 1.2 mL, mean +/- SEM) than in P1 (30.7 +/- 5.5 mL) (P less than 0.01) and in F3 (12.7 +/- 2.1 mL) than in P3 (26.8 +/- 4.4 mL) (P less than 0.05). There was no significant difference between P2 (23.4 +/- 4.6 mL) and F2 (17.5 +/- 3.5 mL). Mean pH values were significantly higher in F1 (6.82 +/- 0.48) than in P1 (3.21 +/- 0.72) (P less than 0.01). No significance was observed between P2 (3.65 +/- 0.62) and F2 (4.53 +/- 0.77), or P3 (3.17 +/- 0.81) and F3 (5.03 +/- 0.80).(ABSTRACT TRUNCATED AT 250 WORDS)

Caffeine-induced block of Na+ current in guinea pig single ventricular cells.

Effects of caffeine on Na+ current (INa) were investigated in single ventricular cells from guinea pigs using the whole cell clamp method. With a Ca(2+)-containing internal solution (pCa 8.2), 10 mM caffeine blocked INa by 17.5 +/- 4.6% at a -120-mV holding potential. It was accompanied by 3- to 5-mV shifts of the steady-state inactivation curve and time constant-voltage relationship toward hyperpolarization. The inactivation kinetics spontaneously shifted toward hyperpolarization at 0.30 +/- 0.17 mV/min. The spontaneous shift was accompanied by a similar negative shift of the threshold potential, whereas caffeine did not affect it. Caffeine retarded the recovery of INa from inactivation, and a 4-mV positive shift in the recovery potential produced a similar retardation in INa recovery without caffeine. The INa block by caffeine was not influenced by reinforcing the internal buffering capacities using internal solutions containing 40 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid or 50 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid or by pretreating the cell with 1 microM ryanodine. Neither pretreatment with isoproterenol or H 7 nor prestimulation of Gs protein by nonhydrolyzable GTP (GTP gamma S) altered the effects of caffeine on INa. It is concluded that caffeine inhibits INa and shifts the inactivation kinetics without being mediated by changes in intracellular ionic composition or intracellular signaling systems. Direct action on the channel proteins may be involved.

Analysis of bites on three-dimensional vectorcardiography after coronary artery ligation in dogs.

The serial changes in the QRS loops of vectorcardiograms were investigated following ligation of a branch of the left anterior descending artery (LAD) by the three-dimensional rotation method in 18 dogs. Concave inflections of the QRS loop, defined as "bites," were best delineated when the loop was viewed from a left cranial or right caudal direction. Bites appeared 48 +/- 8 minutes after LAD ligation in all of the dogs, and their development was closely related to the temporal changes in the % sigma R and QRS point score on a standard 12-lead electrocardiogram. Q waves were not observed on the electrocardiograms in 9 dogs. In the remaining 9, they appeared 117 +/- 18 minutes after LAD ligation. The bite duration, area, and amplitude were compared with the anatomical extent of the infarcts. A significant positive correlation was found between bite duration and infarct size. The detection of bites on the three-dimensionally rotated vectorcardiogram appears to have a high sensitivity for anterior myocardial infarction and could potentially become a useful diagnostic tool.

Block of Na+ channels by imipramine in guinea-pig cardiac ventricular cells.

The effects of imipramine on the Na+ current of guinea-pig ventricular myocytes were examined by the whole-cell clamp method. Imipramine inhibited the Na+ current with a dissociation constant value of 25 microM at a -130 mV holding potential. At 1 microM, imipramine caused a negative shift of the channel availability curve by 4.0 +/- 1.03 mV with its steepness unaffected. The inactivation time constants were not changed by 30 microM imipramine. Paired pulse experiments revealed that imipramine binds to the inactivated Na+ channels with time constants of 3.7 +/- 0.27 sec at -65 mV and 2.4 +/- 0.58 sec at -20 mV, and that it dissociates from the channels with time constants of 5.9 +/- 1.05 sec at -90 mV and 2.0 +/- 0.87 sec at -130 mV. From these paired pulse experiments, the dissociation constant for the interactions between imipramine and inactivated channels was calculated to be 0.67 microM, a value within its therapeutic plasma concentration. These slow interactions of imipramine with inactivated Na+ channels resulted in a slow onset of the frequency-dependent extrablock in the effects of imipramine on the Na+ current. Consequently, the imipramine-induced extrablock sufficient to terminate re-entrant tachyarrhythmias would not develop shortly after their initiation. Short depolarizations of 1- to 3-msec duration sustained appreciable extra blockage when a high concentration of 10 microM imipramine was used, or they were repeatedly applied at a high frequency. However, access of imipramine to the open channels seems to play a minor role in the drug-channel interactions.

Time- and voltage-dependent block of the delayed K+ current by quinidine in rabbit sinoatrial and atrioventricular nodes.

The modes in which quinidine blocks the delayed K+ current (IK) of rabbit sinoatrial and atrioventricular nodes were investigated by voltage clamp experiments using small preparations. Depolarizing pulses were applied from a holding potential of -50 mV and resultant IK current was evaluated. At a concentration of 2 x 10(-6) M, quinidine blocked 52 +/- 5% of IK with a 1000-msec test pulse of 0 mV, whereas it inhibited the slow inward current by only 5 to 10%. IK inhibition was enhanced with increasingly larger depolarizations. The activation curve obtained with the use of 1000-msec test pulses shifted toward hyperpolarization by 3.0 mV and its slope factor increased from 7.3 to 8.8, suggesting a voltage-dependent mechanism for IK blockage. Short and small depolarizing pulses from the holding potential of -50 mV hardly affected II. The activation of IK in the presence of quinidine did not show any delay. These results indicated a low affinity of quinidine to the closed (deactivated) channels. The deactivation time constant of IK was significantly prolonged from 120 to 145 msec at -50 mV. By applying the modulated receptor model to the K+ current, the tail current in the presence of quinidine was well reconstructed when the time constant of drug-channel interactions was 300 msec at -50 mV and 2000 msec at -30 mV. It is suggested that the unblocking of quinidine slows the decay of the IK tail current.

Pulmonary hypertension in a patient with rheumatoid arthritis.

A 53-year-old woman who had suffered from severe rheumatoid arthritis developed pulmonary hypertension. Her small arteries in the lung showed plexogenic arteriopathy with fibrous intimal hyperplasia. There was also vasculitis of the small arteries in other organs and mural thrombosis in the pulmonary stem and abdominal aorta. The plexogenic arteriopathy which was responsible for pulmonary hypertension appears to be the result of vasculitis in association with rheumatoid arthritis.

Sensitivity and accuracy in recording His-Purkinje activity by surface-averaged electrocardiography.

A clinical evaluation of the surface-averaged ECG (SAE) to record His-Purkinje activity (HPA) was made on 70 patients who underwent His bundle electrograms (HBE). The recorded signals first judged as HPA in 43 patients by the noninvasive method alone were later verified in 37 patients by HBE; the accuracy of the HPA recordings (predictive value) was 86.0%. The HPA-V interval measured noninvasively had a high correlation with the HV interval by HBE (r = 0.89, p less than 0.01). The verified detection rate in all 70 patients was 52.9%: HPA was detected in 12 of 18 patients (66.7%) with sclerotic and hypertensive heart disease (Group I), five of 19 patients (26.3%) with rheumatic heart disease (Group II), 11 of 17 patients (64.7%) with congenital heart disease (Group III), and nine of 16 patients (56.2%) with miscellaneous conditions (Group IV). The detection rate was markedly lower in Group II than in other groups (Group II vs Group I or III, p less than 0.025). The PR segment was significantly longer in the patients in whom HPA was detected than in those in whom it was not detected (71.5 +/- 22.3 msec vs 43.9 +/- 19.5 msec, p less than 0.001). His-Purkinje activity (HPA) was detected in 32 of 52 recordings (61.5%) with sinus rhythm and seven of 20 recordings (35.0%) with atrial fibrillation, including two recordings in each of two cardioverted patients (p less than 0.05). We conclude that the surface-averaged ECG (SAE) has clinically acceptable sensitivity and accuracy except in patients with rheumatic heart disease, short PR segments or atrial fibrillations.