CRTH2-dependent, STAT6-independent induction of cedar pollen dermatitis.

BACKGROUND: Airborne contact dermatitis to cedar pollen is a recently identified disease that generally affects individuals with cedar pollinosis of the nasal and/or ocular symptoms, as well as some patients with atopic dermatitis. OBJECTIVE: To elucidate the pathological mechanisms of cedar pollen dermatitis. METHODS: We established a mouse model of cedar pollen dermatitis by epicutaneous sensitization with Japanese cedar pollen antigen (Ag). RESULTS: Histologically, there was marked dermal cellular infiltrate, including eosinophils and mast cells, with epidermal thickening. The induction of dermatitis was accompanied by production of cedar pollen-specific IgE. In the lesional skin, IL-13, IL-18, eotaxin/chemokine (C-C motif) ligand (CCL) 11, regulated upon activation, normal T cell expressed and secreted/CCL5, macrophage-derived chemokine/CCL22 and thymus and activation-regulated chemokine/CCL17, but not IL-4 and IFN-gamma, were produced. Mast cell-deficient WBB6F1-W/W(v) mice failed to develop cedar pollen dermatitis, although regional lymph node cells proliferated in response to Cryptomeria japonica (Cry j) 1 and Cry j2 Ags in vitro. Surprisingly, the induction of dermatitis was independent of STAT6/IgE. In contrast, mice deficient in CRTH2, a receptor for prostaglandin D2 (PGD2), showed diminished inflammation. Consistent with this, ramatroban, a CRTH2 antagonist, significantly inhibited inflammatory cell infiltration. CONCLUSION: These data suggest that PGD2-CRTH2 signalling contributes to inflammation in cedar pollen dermatitis, and unlike cedar pollinosis of the nasal mucosa, STAT6 is not a therapeutic target for treatment.

Functional characterization of Musca glutamate- and GABA-gated chloride channels expressed independently and coexpressed in Xenopus oocytes.

Ligand-gated chloride channels (LGICs) are important targets for insecticides and parasiticides. Genes encoding subunits of two LGICs, a glutamate-gated chloride channel (MdGluCl-alpha) and a gamma-aminobutyric acid (GABA)-gated chloride channel (MdRdl), were cloned from house-flies (Musca domestica L.). These genes were first expressed independently in Xenopus laevis oocytes by cRNA injection in order to investigate the pharmacology of these ligand-gated channels using two-electrode voltage-clamp electrophysiology. It was found that L-glutamate and GABA activated the MdGluCl-alpha homo-oligomers with an EC(50) value of 30 microM and the MdRdl homo-oligomers with an EC(50) value of 101 microM, respectively. Both channels were chloride ion-permeable, and the MdRdl channel was more sensitive to chloride channel blockers, such as gamma-hexachlorocyclohexane (gamma-HCH), fipronil and picrotoxinin, than the MdGluCl-alpha channel. MdGluCl-alpha required only 1-2 days of incubation after cRNA injection to be expressed in oocytes, whereas 4-7 days of incubation was necessary to achieve MdRdl expression. However, when the cRNA of MdGluCl-alpha was injected at a dose of 1% (w/w) 1 day after the injection of the cRNA of MdRdl, a significant increase in the current amplitude of responses to GABA was observed, and the incubation period necessary for MdRdl expression became shorter. These results suggest that MdGluCl-alpha assists in the expression of MdRdl when the two are coexpressed.

Cardiovascular response to epinephrine-containing local anesthesia in patients with cardiovascular disease.

OBJECTIVE: The purpose of the present study was to examine the safety of epinephrine-containing local anesthesia for use on patients with cardiovascular disease. STUDY DESIGN: Twenty-seven patients with cardiovascular disease were studied. The cardiac functional capacity of 9 patients was New York Heart Association class I; 11, class II; and 7, class III. Hemodynamic responses to intraoral injection of 1.8 mL of 2% lidocaine with 1:80,000 epinephrine were measured with impedance cardiography. RESULTS: Systolic blood pressure and heart rate increased by 4.1% and 5.1%, respectively, immediately after the lidocaine-epinephrine injection. Consequently, rate pressure product increased by 10.0%. Cardiac index increased by 14.2%, and total peripheral resistance decreased by approximately 10%. No patient complained of cardiac symptoms. There were no significant differences in hemodynamic responses related to the extent of the cardiac functional capacity. CONCLUSION: We concluded that lidocaine-epinephrine was safe and had few, if any, hemodynamic consequences in patients with cardiovascular disease.

Cardiovascular responses to epinephrine-containing local anesthetics for dental use: a comparison of hemodynamic responses to infiltration anesthesia and ergometer-stress testing.

OBJECTIVE: Cardiovascular effects of infiltration anesthesia have been documented in numerous studies. However, few studies have been carried out to compare the effects of infiltration anesthesia with the effects of exercise-stress testing. The purpose of this study was to examine this issue. STUDY DESIGN: Eight young and 13 older subjects were given infusions of epinephrine to produce cardiovascular responses comparable with those found in subjects undergoing infiltration anesthesia with 3.6 mL of lidocaine with 1:80,000 epinephrine (L-E). Cardiovascular responses to this drug treatment were evaluated with echocardiography and compared with those produced by ergometer exercise. RESULTS: The hemodynamic effects of L-E infiltration anesthesia were less than those produced by ergometer-stress testing at 25 watts (W) in young subjects and at 15 W in the older subjects. The workload of this ergometer-stress testing was about 4 metabolic equivalents (METS), which is approximately equivalent to the workload of walking 4.8 km/hr, doing light yard work (ie, raking leaves, weeding, or pushing a power mower), painting, or doing light carpentry. CONCLUSION: With the exception of some specific pathologic conditions, such as serious arrhythmia, infiltration anesthesia with 3.6 mL of L-E can be carried out safely on the patients who have exercise capacity of more than 4 METS.

Safety of dental treatment in patients with previously diagnosed acute myocardial infarction or unstable angina pectoris.

OBJECTIVE: The purpose of this study was to assess the safety of invasive dental treatments, such as tooth extraction and pulpectomy under local anesthesia, in patients with unstable angina pectoris and within 6 months after onset in patients who had experienced acute myocardial infarction. STUDY DESIGN: Cardiovascular complications during and after dental treatment and preoperative risk factors were explored in 63 patients who had experienced unstable angina pectoris or acute myocardial infarction. RESULTS: A total of 79 dental treatments were performed with no intraoperative complications. Chest pain occurred in 8 patients within 1 week after dental treatment. Risk factors for postoperative complications were identified as a history of chest pain within 2 weeks before the dental treatment and failure to clear the Master Test Single stress test. CONCLUSIONS: Many patients who had experienced unstable angina pectoris or acute myocardial infarction tolerated dental treatment when appropriate stress control measures were used. However, approximately 10% of the patients experienced postoperative problems. Acceptability of dental treatment should be determined on the basis of the comprehensive assessment of each patient.

Mistletoe lectin I forms a double trefoil structure.

The quaternary structure of mistletoe lectin I (MLI), a type II ribosome inactivating protein, has been determined by X-ray crystallography. A definitive molecular replacement solution was determined for MLI using the co-ordinates of the homologue ricin as a search model. MLI exists as an [AB]2 dimer with internal crystallographic two-fold symmetry. Domain I of the B chains is non-covalently associated through interactions involving three looped chains (alpha, beta, gamma) in each molecule of the dimer, forming a double trefoil structure. The ricin molecule which shares 52% sequence homology with MLI has a disulphide bridge between Cys20 and Cys39 in the alpha loop. An evolutionary mutation has replaced Cys39 with serine in MLI. This mutation appears to allow the alpha loop the flexibility required to take up its place at the dimer interface, and also suggests a rationale for why ricin does not form dimers. Measurement of retention times using FPLC gel filtration confirms that dimerisation also occurs in solution between MLI B chains with an association constant Ka = 10(6) M.

Deep hypothermic intermittent circulatory arrest--an adjunct technique for operations on aneurysms involving the aortic arch.

Aneurysms involving the aortic arch were repaired in 12 patients using a technique known as deep hypothermic intermittent circulatory arrest (DHICA). This technique consists of repeated cycles of 20 min of circulatory arrest and 10 min of cerebral and systemic reperfusion. Aneurysms were of the following types: 2 true atherosclerotic aneurysm, 8 aortic dissections, and 2 traumatic aneurysm. There were 2 operative deaths caused by coagulopathy as a result of hepatic failure and difficulty with left ventricular venting. The frequency of circulatory arrest ranged from 2 to 5 cycles, and total circulatory arrest ranged from 20 to 71 min (mean 43.6 min). The lowest tympanic temperature ranged from 17.7 to 19.2 degrees C. No permanent cerebral complications occurred in 10 patients. We believe that this adjunct technique offers excellent results in the surgical treatment of aneurysms involving the aortic arch.

Chemical nature of the light emitter of the Aequorea green fluorescent protein.

The jellyfish Aequorea victoria possesses in the margin of its umbrella a green fluorescent protein (GFP, 27 kDa) that serves as the ultimate light emitter in the bioluminescence reaction of the animal. The protein is made up of 238 amino acid residues in a single polypeptide chain and produces a greenish fluorescence (lambda max = 508 nm) when irradiated with long ultraviolet light. The fluorescence is due to the presence of a chromophore consisting of an imidazolone ring, formed by a post-translational modification of the tripeptide -Ser65-Tyr66-Gly67-. GFP has been used extensively as a reporter protein for monitoring gene expression in eukaryotic and prokaryotic cells, but relatively little is known about the chemical mechanism by which fluorescence is produced. To obtain a better understanding of this problem, we studied a peptide fragment of GFP bearing the chromophore and a synthetic model compound of the chromophore. The results indicate that the GFP chromophore consists of an imidazolone ring structure and that the light emitter is the singlet excited state of the phenolate anion of the chromophore. Further, the light emission is highly dependent on the microenvironment around the chromophore and that inhibition of isomerization of the exo-methylene double bond of the chromophore accounts for its efficient light emission.

The interaction between pindolol and epinephrine contained in local anesthetic solution to the left ventricular diastolic filling velocity in normal subjects.

To evaluate the interaction between the nonselective beta-blocker, pindolol, and epinephrine contained in a local anesthetic solution, the left ventricular diastolic filling velocity was examined with pulsed Doppler echocardiography. Arterial blood pressure (BP), the R-R interval on the electrocardiogram (RR), and Doppler echo-cardiographic measurements were recorded in seven healthy volunteers after 45 micrograms of epinephrine contained in lidocaine (L-E) was injected in the maxilla after pretreatment with 5 mg of pindolol. The administration of L-E caused the elevation of BP and an increase in RR interval. Peak early (E) and peak atrial (A) filling velocities decreased, whereas isovolumic relaxation time (IVRT) and diastolic filling period (DFP) were prolonged. Although the ratio of E to A (E/A) remained unchanged, E/A/DFP was reduced. In contrast, when L-E was given without pindolol pretreatment, RR interval was shortened and BP was unchanged. The increase of both E and A velocities and the shortening of both IVRT and DFP were observed. E/A remained unchanged but E/A/DFP was increased. These results suggested that L-E caused opposite effects on the left ventricular filling velocity in the presence or absence of pindolol. We conclude that epinephrine activates the left ventricular relaxation rate but impairs it in the presence of pindolol.

The effect of furosemide on evoked otoacoustic emissions in guinea pigs.

After recording transiently evoked otoacoustic emissions (TEOAEs) to a click stimulus in guinea pigs by using the IL088 which was developed by Bray and Kemp (1987) for easy recording and analysis of TEOAE, the changes after intravenous administration of furosemide (30 mg/kg or 50 mg/kg) were examined. The wave of the TEOAE could be detected from 20 of 24 ears (83%). After the i.v. injection of furosemide (30 mg/kg), TEOAE powers (total echo power and highest peak power in FFT pictures) decreased quickly and showed minimum values after 5-10 min. Then they increased rapidly and recovered normally within 60 min after injection. However, no ears showed TEOAEs during the 5- to 10-min period following the injection of the 50-mg/kg dose of furosemide. They then recovered slowly as compared with the group treated with the lower dose of furosemide (30 mg/kg). These changes are similar to those of the endocochlear potential (EP) after furosemide injection. These data support the notion that the EP can contribute to the mechanism of TEOAE generation.

The effects of epinephrine and norepinephrine administered during local anesthesia on left ventricular diastolic function.

To evaluate the effects of epinephrine (E) and norepinephrine (NE) administered during local anesthesia on left ventricular diastolic function, we examined transmitral inflow patterns with pulsed Doppler echocardiography. Arterial blood pressure, heart rate, and transmitral inflow patterns were measured in 10 healthy volunteers when 3.6 mL of 2% lidocaine containing 1:80,000 E or 1:25,000 NE was injected supraperiosteally in the maxilla. The dosage of drug administered was 45 micrograms for E and 144 micrograms for NE. After the administration of E, heart rate was increased, but blood pressure was unchanged. Peak early velocity (R), peak atrial velocity (A), the ratio of A to R (A/R), and the deceleration rate (Dc) were increased, whereas the isovolumic relaxation time (IVRT) was shortened. The increase of R and Dc and the shortening of IVRT indicated an activation of left ventricular relaxation. After the administration of NE, blood pressure was increased and heart rate was decreased. A decrease in Dc, shortening of the acceleration half-time (AcT), and prolongation of IVRT were observed. These changes reflect impeded myocardial relaxation. We conclude that E activates left ventricular diastolic function and that NE, in contrast, impairs it.

[Diarrhea and biogenic amines: regional changes in brain histamine concentration and serotonin metabolism following castor oil-induced diarrhea in rats].

Regional changes in concentrations of histamine (HA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the rat brain were investigated after diarrhea induced by castor oil. Significant decreases in body weight were observed from the 3rd day after daily oral administration of castor oil (2.5 ml/kg). HA concentrations in most brain regions decreased in diarrhea induced by a single administration of castor oil. A significant decrease was recognized particularly in the case of the hippocampus. The influence has begun to appear in the thalamus and hypothalamus in consecutive (3 d) administration. HA concentration in the striatal and hypothalamic regions of the rat treated with castor oil for 9 d significantly decreased in comparison with the control group. On the other hand, an inhibition of 5-HT turnover was observed in the thalamus at 3 h after a single administration of castor oil. However, this inhibition was not found in rats treated with castor oil for 3 d. Moreover, 5-HT concentration in the midbrain significantly decreased in rats that acquired the adaptability for the occurrence of diarrhea. These data present a new finding that the occurrence of diarrhea or acquisition of adaptability for diarrheal occurrence affects the central histaminergic or serotonergic neuron system.

[A case of retroperitoneal chylous cyst developed after cholecystectomy and choledochotomy].

A 43-year-old woman complaining of upper abdominal pain was referred to our clinic. Well movable mass was detected in the right hypochondria region by palpation. Three years before, she underwent cholecystectomy and choledochotomy for cholelithiasis. After that she had been aware of painless mass in the right hypochondria region, but because of no symptom she regarded it as operative scar and had no treatment. Abdominal CT, ultrasonography, upper GI series and barium enema revealed a retroperitoneal cyst compressing the 3rd portion of the duodenum upward and the vena cava backward. Laparotomy showed an unilocular chylous cyst, 5 cm in diameter in the retroperitoneal cavity. Histologically, the cyst was cystic lymphangioma. Etiologically, the previous operation of cholecystocholedocholithiasis was supposed to be a trigger of the development of the chylous cyst.

Effect of chlorpheniramine on muricide induced by thiamine deficiency: pharmacokinetic and behavioral studies.

Chlorpheniramine (5-10 mg/kg) showed a dose-dependent suppressive effect on muricide induced by thiamine deficiency at 1 hr after oral administration. The ED50 value for muricidal suppression was about 7.1 mg/kg (95% confidence limits, 5.4-9.3 mg/kg). The maximum effect of muricidal suppression lasted for 1-2 hr after oral dosage (10 mg/kg). Chlorpheniramine was detectable at 10 min in the blood and brain of thiamine deficient killer-rats by using a high-performance liquid chromatographic method. Maximum brain and blood levels of chlorpheniramine appeared at 45 and 60 min, respectively. In terms of regional distribution, the highest levels were measured in the limbic system, especially in the hippocampus. Although neither blood nor brain levels of chlorpheniramine reflect its pharmacological activity, it can easily enter the brain and suppress muricide more potently than imipramine.

Reproduction of acute bracken poisoning in a calf with ptaquiloside, a bracken constituent.

Acute bracken fern toxicity in a calf was reproduced with ptaquiloside, a norsesquiterpene glucoside, isolated from the boiling water extract of bracken fern. Ptaquiloside was dissolved in 500 ml of saline and administered by drench at increasing dosages for six days out of every seven for the following periods: 400 mg/day for 24 days, 800 mg/day for 14 days and 1600 mg/day for four days. Neutrophilic granulocytes began to decrease markedly around 50 days after the start of the experiment, and granulocytopenia continued for a further 35 days until the autopsy, despite the discontinuance of ptaquiloside administration. Thrombocytes showed a relatively slow depression and reached 1 X 10(5)/mm3 at the lowest level. The calf was autopsied 86 days after the start of administration of ptaquiloside. Sternal bone marrow was found to be mostly replaced with fat marrow and only small foci of erythropoietic cells and a small number of megakaryocytes remained.

Hyperplastic nodules of the liver induced in rats fed bracken diet.

Hyperplastic nodules (HN) of the liver were induced in Charles River Sprague-Dawley rats (CD rats) and ACI rats fed a diet containing 30% bracken for 260 and 180 days, respectively. HN were also induced in high incidence in CD rats fed a diet containing the carcinogenic fractions of bracken extract.