Adverse event profiles of hypomagnesemia caused by proton pump inhibitors using the Japanese Adverse Drug Event Report (JADER) Database.

Proton pump inhibitors (PPIs) are commonly used for the prevention or treatment of gastric ulcers, but they can induce hypomagnesemia. Little is known about the onset duration and risk factors related to patient characteristics of this adverse event in Japanese patients. Therefore, we analyzed the time-to-onset of PPI-induced hypomagnesemia and evaluated the association between hypomagnesemia and PPIs using the Japanese Adverse Drug Event Report (JADER) database. We analyzed hypomagnesemia cases between 2004 and 2021. The time-to-onset analysis was performed using the Weibull distribution, and the adjusted reporting odds ratio (aROR) or 95% confidence interval (95% CI) was calculated using a multiple logistic regression analysis. The analysis database comprised 236,525 cases, with 188 cases associated with hypomagnesemia. The median onset duration (interquartile range) of PPI-induced hypomagnesemia was 99.0 (51.8-285.5 ) days, which is considered the random failure type. The multiple logistic regression analysis revealed that hypomagnesemia is significantly associated with male sex (aROR, 95% CI: 1.66, 1.23-2.25) , age < 60 (1.59, 1.14-2.21) , estimated body-mass index (eBMI) (0.94, 0.91-0.98) , PPIs (1.66, 1.18-2.30) , and the interaction of age (<60)*PPIs (1.58, 1.13-2.19) . However, diuretics were not significantly associated with hypomagnesemia. Our results suggest that serum magnesium levels should be measured regularly regardless of the duration of PPI use, especially in patients with male sex, age < 60, or low BMI. These findings will assist health professionals in the adequate use of PPIs. These findings need to be evaluated by cohort studies and long-term clinical investigations.

Time-dependent changes in serum magnesium levels in patients receiving cetuximab with low baseline serum sodium levels.

Cetuximab causes electrolyte abnormalities, such as hypomagnesemia, hypokalemia, and hypocalcemia. However, little is known about the relationships between the onset of hypomagnesemia, patient background before administration, and time-dependent changes in serum magnesium levels. Therefore, we examined the patient backgrounds that influenced the onset of hypomagnesemia and the time-dependent changes in serum magnesium levels in patients receiving cetuximab. A retrospective study was performed to investigate patients with advanced or recurrent colorectal cancer or head and neck cancer, treated with a cetuximab regimen from 2012 to 2020 at Kindai University Nara Hospital. In total, 52 patients who met the inclusion criteria were enrolled in this study. The serum magnesium level was significantly lower in the hyponatremia before the administration group than in the non-hyponatremia group (p < 0.001). Univariate logistic regression analysis revealed that the baseline serum sodium levels (odds ratio [OR]: 0.741, 95% confidence interval [CI]: 0.588-0.934) and the combination of magnesium oxide tablet (OR: 0.997, 95% CI: 0.995-0.999) were one of the independent factors for hypomagnesemia. These results indicated that hyponatremia before administration may be an indicator of serum magnesium levels after administration of cetuximab. Cetuximab-induced hypomagnesemia may be predicted using baseline serum sodium levels, and hypomagnesemia may be prevented by administration of magnesium oxide tablets. Our findings provided new evidence for the management of serum magnesium levels in patients receiving cetuximab.

Search for K_{L}→π

A search for the rare decay K_{L}→π^{0}νν[over ¯] was performed. With the data collected in 2015, corresponding to 2.2×10^{19} protons on target, a single event sensitivity of (1.30±0.01_{stat}±0.14_{syst})×10^{-9} was achieved and no candidate events were observed. We set an upper limit of 3.0×10^{-9} for the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level (C.L.), which improved the previous limit by almost an order of magnitude. An upper limit for K_{L}→π^{0}X^{0} was also set as 2.4×10^{-9} at the 90% C.L., where X^{0} is an invisible boson with a mass of 135 MeV/c^{2}.

Nuclear accumulation of annexin A2 contributes to chromosomal instability by coilin-mediated centromere damage.

Most human cancers show chromosomal instability (CIN), but the precise mechanisms remain uncertain. Annexin A2 is frequently overexpressed in human cancers, and its relationship to tumorigenesis is poorly understood. We found that annexin A2 is overexpressed in the nuclei of CIN cells compared with cells with microsatellite instability (MIN). Ectopic annexin A2 expression in MIN cells results in a high level of aneuploidy and induces lagging chromosomes; suppression of annexin A2 in CIN cells reduces such CIN signatures with apoptosis of highly aneuploid cells. Ectopic expression of annexin A2 in MIN cells reduces the expression of centromere proteins. Conversely, annexin A2-knockdown in CIN cells increases the expression of centromere proteins. Moreover, the endogenous expression levels of centromere proteins in CIN cells were greatly reduced compared with MIN cell lines. The reduced expression of centromere proteins likely occurred due to aberrant centromere localization of coilin, a major component of the Cajal bodies. These results suggest that nuclear accumulation of annexin A2 has a crucial role in CIN by disrupting centromere function.

Activation of OASIS family, ER stress transducers, is dependent on its stabilization.

Endoplasmic reticulum (ER) stress transducers transduce signals from the ER to the cytoplasm and nucleus when unfolded proteins accumulate in the ER. BBF2 human homolog on chromosome 7 (BBF2H7) and old astrocyte specifically induced substance (OASIS), ER-resident transmembrane proteins, have recently been identified as novel ER stress transducers that have roles in chondrogenesis and osteogenesis, respectively. However, the molecular mechanisms that regulate the activation of BBF2H7 and OASIS under ER stress conditions remain unresolved. Here, we showed that BBF2H7 and OASIS are notably unstable proteins that are easily degraded via the ubiquitin-proteasome pathway under normal conditions. ER stress conditions enhanced the stability of BBF2H7 and OASIS, and promoted transcription of their target genes. HMG-CoA reductase degradation 1 (HRD1), an ER-resident E3 ubiquitin ligase, ubiquitinated BBF2H7 and OASIS under normal conditions, whereas ER stress conditions dissociated the interaction between HRD1 and BBF2H7 or OASIS. The stabilization of OASIS in Hrd1(-/-) cells enhanced the expression of collagen fibers during osteoblast differentiation, whereas a knockdown of OASIS in Hrd1(-/-) cells suppressed the production of collagen fibers. These findings suggest that ER stress stabilizes OASIS family members and this is a novel molecular mechanism for the activation of ER stress transducers.

Prediction of recurrence after laparoscopic fundoplication for erosive reflux esophagitis based on anatomy-function-pathology (AFP) classification.

BACKGROUND: The usefulness of the anatomy-function-pathology (AFP) score was examined to evaluate its prediction of recurrence after laparoscopic fundoplication for erosive reflux esophagitis. METHODS: Of the patients undergoing laparoscopic fundoplication for erosive reflux esophagitis of Los Angeles classification grade A or higher from December 1994 to December 2004, 107 who underwent preoperative barium esophagogram, pH monitoring, and endoscopy were selected as subjects. The AFP score was calculated by A, F, and P factor grades of the AFP classification. By comparing patients with and without recurrence, the usefulness of the AFP score for predicting recurrence was examined. RESULTS: Reflux esophagitis recurred in seven patients. No significant difference in age, sex, or A or F factor was observed between the groups, whereas a significant difference was observed in the P factor (p = 0.008). On the other hand, the mean AFP score in the recurrence group was 16.9 +/- 5.3, whereas that in the nonrecurrence group was 8.9 +/- 5.3 (p = 0.0021). Among the patients with a score of 17 points or more (n = 23), recurrence was found in 6 patients (26%). On the other hand, among the patients with a score lower than 17 points (n = 84), recurrence was found in 1 patient, but not in the remaining 83 patients (1%). Sensitivity was thus 85.7% (95% confidence interval [CI], 42.1-99.6), and specificity was 83% (95% CI, 74.2-89.8). The positive predictive value was 26.1% (95% CI, 10.2-48.4), and the negative predictive value was 98.8% (95% CI, 93.5-99.9). Multiple logistic regression analysis was performed, and receiver operating characteristics curves were obtained. The area under the curve for the AFP score was 0.8457, whereas that for the P factor was 0.7907 (p = 0.0045), suggesting that the AFP score may more accurately predict recurrence than the P factor. CONCLUSION: The AFP score may be useful for predicting postoperative recurrence. If surgery is performed when the AFP score is lower than 17 points, the likelihood of postoperative recurrence is expected to be very low.

Survival impact of epidermal growth factor receptor overexpression in patients with non-small cell lung cancer: a meta-analysis.

BACKGROUND: It is thought that overexpression of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) might compromise patient survival, presumably by promoting tumour growth by an autocrine mechanism. However, conflicting results have been reported from various laboratories, and the clinical importance of EGFR overexpression remains unsettled. METHODS: A meta-analysis of previous studies was performed to quantitatively review the effects of EGFR overexpression on survival in patients with NSCLC using a DerSimonian-Laird random effects model. Eighteen studies including 2972 patients were subjected to final analysis. RESULTS: Overall, positivity for EGFR overexpression differed between histological types: 39% in adenocarcinomas, 58% in squamous cell carcinomas, 38% in large cell carcinomas, and 32% in cancers in a miscellaneous category (p<0.0001). The combined hazard ratio (HR) was 1.14 (95% CI 0.97 to 1.34; p = 0.103), indicating that EGFR overexpression has no significant impact on survival. When only the 15 immunohistochemistry based studies were considered, the combined HR was 1.08 (95% CI 0.92 to 1.28; p = 0.356), again suggesting that EGFR overexpression has no impact on survival. Heterogeneity testing indicated that there was heterogeneity between studies but publication bias was absent, which suggests that the summary statistics obtained may approximate the actual average. CONCLUSIONS: EGFR overexpression was not associated with poorer survival in patients with NSCLC. Specific mutations of the EGFR gene will need further study in terms of survival implications.

Laparoscopic Heller myotomy and Dor fundoplication for the treatment of achalasia. Assessment in relation to morphologic type.

BACKGROUND: The significance of laparoscopic Heller myotomy and Dor fundoplication (LHD) for the treatment of achalasia in relation to the severity of the lesion has not been sufficiently assessed. METHODS: Of patients who were diagnosed with achalasia from August 1994 to February 2004, 55 individuals who underwent LHD served as subjects. The therapeutic effects of LHD were assessed in terms of operation time, intraoperative complications, postoperative hospital stay, and symptom improvement in relation to morphologic type (spindle type, Sp; flask type, Fk; and sigmoid type, Sig). Degree of symptomatic improvement was classified into four grades: excellent, good, fair, and poor. RESULTS: Breakdown of morphologic type was as follows: Sp, n = 29; Fk, n = 18; and Sig, n = 8. Excluding one patient for whom conversion to open surgery was required, median average operation time for 54 patients was 160 min. As to intraoperative complications, esophageal mucosal perforation was seen in nine of the 55 patients (16%); however, conversion to open surgery could be avoided by suturing the affected area. Moreover, intraoperative bleeding of at least 100 g was seen in five of the 55 patients (9%), with one Fk patient requiring conversion to open surgery and transfusion. Median postoperative hospital stay was 8 days. Degree of dysphagia relief was excellent in 45 patients (83%), good in eight patients (15%), and fair in one patient (2%). Excellent improvement was obtained in 90%, 88%, and 50% in Sp, Fk, and Sig patients, respectively. Reflux esophagitis was seen in two patients, and was treated with a proton pump inhibitor. CONCLUSIONS: The results of the present study suggest that classification of morphologic type is a useful parameter in predicting postoperative outcome in achalasia. In order to achieve excellent symptomatic relief, surgery for achalasia should be recommended for but not limited to Sp and Fk types.

Hand-assisted laparoscopic and thoracoscopic surgery (HALTS) in radical esophagectomy with three-field lymphadenectomy for thoracic esophageal cancer.

AIM: To prove the feasibility of hand-assisted laparoscopic and thoracoscopic surgery (HALTS) for radical esophagectomy with three-field lymphadenectomy to thoracic esophageal cancer. METHODS: Esophagectomy with three-field lymphadenectomy was performed using HALTS in 19 patients with thoracic esophageal cancer without distant metastasis. Five patients had chemo-radiotherapy prior to surgery. RESULTS: All operations were completed successfully without the need for open surgery. Mean surgical time was 476+/-58 min, and mean blood loss during surgery was 343+/-184 mL. All patients started tube feeding and were moved from the intensive care unit to the general surgery ward the day after surgery. Discharge occurred a median of 10 days after surgery. Fifteen patients could return to full time jobs from 8 to 62 days after surgery (median 22 days) and from 1 to 35 days after discharge (median 9 days). Other three could return to daily activities at home soon as well. No major complications occurred, except one anastomotic leak. In terms of lung function, %FEV(1) was not changed whereas %VC was reduced significantly 1 month after surgery. All but two recurrences have been healthy without a relapse for a mean of 289 days. CONCLUSIONS: These results suggest that HALTS may be a useful surgical technique to reduce the invasiveness of conventional radical esophagectomy with three-field lymphadenectomy for thoracic esophageal cancer.

Survival following lobectomy vs limited resection for stage I lung cancer: a meta-analysis.

Extent of resection needed to treat lung cancer has long been an issue. The sole randomised controlled trial, reported by the Lung Cancer Study Group, advised against limited resection as standard surgery even for small peripheral non-small-cell lung cancers (< or =3 cm), because of frequent local recurrences. Elsewhere, conflicting results have been reported from different institutions. We therefore conducted a meta-analysis of reported studies to compare survival of stage I patients between limited resection and standard lobectomy. A MEDLINE web search for computer-archived bibliographic data yielded 14 articles suitable for analysis. Combined survival differences (survival rate with lobectomy minus that with limited resection) at 1, 3, and 5 years after resection according to the DerSimonian-Laird random effects model were 0.7% (95% CI, -0.8 to 2.1; P=0.3659), 1.9% (95% CI, -3.7 to 7.4; P=0.5088), and 3.6% (95% CI, -0.4 to 10.5; P=0.3603), respectively. None of these survival differences were significant, indicating that survival after limited resection for stage I lung cancer was comparable to that after lobectomy. However, since interstudy heterogeneity was detected, caution is required in interpretation of the results.

Excision of pseudotumour in a patient with haemophilia A and inhibitor managed with recombinant factor VIIa.

We describe a patient with haemophilia A and factor VIII inhibitor who underwent surgical excision of a large pseudotumour in the left femoral region. Haemostasis was successfully maintained with bolus doses of recombinant factor VIIa at 2-h intervals and anti-fibrinolytic therapy, and the pseudotumour was removed. Subsequently, the dose interval was gradually prolonged to 8 h for a total of 18 days. Although a spontaneous haemorrhage was observed on postoperative day 8, haemostasis was achieved by reducing the dosage interval. No adverse event occurred during the course of treatment.

Morphological change of the micelle of poly(styrene)-b-poly(2-vinylpyridine)-b-poly(ethylene oxide) induced by binding of sodium dodecyl sulfate.

Morphological change of a micelle of poly(styrene)-b-poly(2-vinylpyridine)-b-poly(ethylene oxide) (PS-PVP-PEO) polymer was induced by binding sodium dodecyl sulfate (SDS) to the PVP block in acidic aqueous solutions. The change in the size of SDS/PS-PVP-PEO complexes was detected by dynamic light scattering measurements and atomic force microscopy, and the binding of SDS was confirmed by zeta-potential measurements. When the micelle was free from SDS in acidic aqueous solutions, the hydrodynamic diameter of the micelle was 216 nm, reflecting the extended conformation of the PVP block due to the repulsion between protonated pyridine units. As the cationic PVP block was electrically neutralized with anionic SDS, the diameter was gradually reduced concomitant with the decrease in zeta-potential and finally reached 175 nm when the PVP block was completely neutralized. The decrease in the diameter shows the morphological change of the PVP block from extended to shrunken forms. Further addition of SDS did not cause the changes of the diameter nor zeta-potential. This indicates that SDS was not bound to the PS-PVP-PEO polymer after the PVP block was fully neutralized and that the hydrophobic binding of SDS to the polymer was negligible due to the low concentration of SDS.

Endothelin protein expression as a significant prognostic factor in oesophageal squamous cell carcinoma.

The aim of this study was to investigate if the expression of endothelin (ET), a vasoactive peptide, in cancerous oesophageal lesions, adjacent dysplastic tissue and normal mucosa might be prognostic. Tissue samples from a total of 101 patients with oesophageal squamous cell carcinoma were obtained and stained with ET antibody in an immunohistochemical analysis. High staining levels of ET within normal mucosa were related to lymph vessel invasion, regional lymph node metastasis and distant metastasis, as well as a reduced relapse-free survival (log-rank test; P=0.0066). After adjustment for several histological prognostic risk factors and each component of the TNM classification system, high ET expression within dysplastic tissue more than doubled the hazard ratio of relapse with significant model improvement. These results suggest that, in addition to known histological risk factors and TNM classification criteria, measurement of ET expression with a simple immunohistochemical analysis might further help in predicting the prognosis of patients with oesophageal squamous cell carcinoma.

Three new alleles of IGHG2 and their prevalence in Danish Caucasians, Mozambican Blacks and Japanese.

The human IGHG2 gene locus is polymorphic, encoding two known allotypes of IgG2: G2m(n-) and G2m(n+). The allele prevalence varies greatly between different ethnic groups and individual genotypes correlate with the level of plasma IgG2 and with antibody responses to certain polysaccharide antigens. In this study, we present three new alleles of IGHG2 (IGHG2*03, 04, and 05), and a complete sequence specific PCR typing system allowing discrimination between the different allotypes of IgG2. A hitherto unknown allotype, which we name G2m(ny), is encoded by IGHG2*04 and differs from G2m(n-) by asparagine rather than serine in CH1 residue 75 and by phenylalanine rather than leucine in CH1 residue 76 (EU numbering 192 and 193). The polymorphic residues are probably surface exposed near the hinge region. The same residues are also found in IgG1, IgG3, and IgG4, and G2m(ny) is therefore an isoallotype that probably arises by gene conversion within the heavy chain locus. The IGHG2*04 allele is present among Danish Caucasians with a low prevalence (2.5%), but was not found in Japanese or Mozambicans. The two other new alleles (IGHG2*03 and IGHG2*05) both encode the G2m(n-) allotype. The IGHG2*03 allele encodes most of the IgG2 of the G2m(n-) allotype in Danish Caucasians.

Percutaneous absorption of non-steroidal anti-inflammatory drugs from in situ gelling xyloglucan formulations in rats.

The potential of gels formed in situ by dilute aqueous solutions of a xyloglucan polysaccharide derived from tamarind seed as sustained release vehicles for percutaneous administration of non-steroidal anti-inflammatory drugs has been assessed by in vitro and in vivo studies. Chilled aqueous solutions of xyloglucan that had been partially degraded by beta-galactosidase formed gels at concentrations of 1-2% w/w when warmed to 37 degrees C. The in vitro release of ibuprofen and ketoprofen at pH 7.4 from the enzyme degraded xyloglucan gels and the subsequent permeation of these fully ionized drugs through cellulose membranes followed root-time kinetics over a period of 12 h after an initial lag period. Diffusion coefficients were appreciably higher when the drugs were released from 1.5% w/w xyloglucan gels than when released from 25% w/w Pluronic F127 gels formed in situ under identical conditions. The difference in release rates was attributed to differences in the structure of the gels. The permeation rate of ibuprofen through excised skin was higher than that of ketoprofen when released from both gels, but of similar magnitude through cellulose membranes. Plasma concentrations of ibuprofen and ketoprofen from gels formed in situ following topical application of chilled aqueous solutions of xyloglucan and Pluronic F127 to the abdominal skin of rats were compared. The bioavailabilities of ibuprofen and ketoprofen were significantly higher when released from xyloglucan gels compared to Pluronic F127 gels. Occlusive dressing techniques had a greater enhancing effect on the bioavailability of ibuprofen when released from Pluronic gels.

Ganglioside GD1a inhibits HGF-induced motility and scattering of cancer cells through suppression of tyrosine phosphorylation of c-Met.

We previously reported that ganglioside GD1a, which is highly expressed in poorly metastatic FBJ-S1 cells, inhibits the serum-induced motility of FBJ-LL cells and that the metastatic potential of FBJ-LL cells is completely suppressed by enforced GD1a expression (Hyuga et al., Int J Cancer 1999;83:685-91). We recently discovered that hepatocyte growth factor (HGF) induces FBJ-LL cell motility. In the present study, the HGF-induced motility of FBJ-S1 cells was found to be one-thirtieth that of FBJ-LL cells. This motility of GD1a-expressing transfectants, which were produced by transfection of FBJ-LL cells with GM2/GD2 synthase cDNA, decreased with increases in their GD1a expression and HGF induced almost no motility in GD1a-pretreated FBJ-LL cells, indicating that GD1a inhibits the HGF-induced motility of FBJ-LL cells. The expression of the HGF receptor c-Met on FBJ-S1 cells, FBJ-LL cells, transfectants and a mock-transfectant was almost the same. The level of tyrosine phosphorylation of c-Met after HGF stimulation in FBJ-S1 cells, GD1a-pretreated FBJ-LL cells and a GD1a-expressing transfectant was significantly lower than in FBJ-LL cells and a mock-transfectant. These findings suggested that GD1a inhibits the HGF-induced motility of FBJ-LL cells through suppression of tyrosine phosphorylation of c-Met. HepG2 cells, a human hepatoma cell line, were used to investigate whether GD1a interferes with other cancer cells expressing c-Met. HepG2 cells did not express GD1a. HGF induced cell scattering of HepG2 cells and the scattering was inhibited by pretreating the cells with GD1a. The c-Met in the cells was autophosphorylated by stimulation with HGF, but after treating the cells with GD1a, the HGF-induced autophosphorylation of c-Met was suppressed. These results suggest that GD1a acts as a negative regulator of c-Met in cancer cells.

Oral sustained delivery of theophylline from thermally reversible xyloglucan gels in rabbits.

Thermally reversible gels formed in-situ following the oral administration of dilute aqueous solutions of an enzyme-degraded xyloglucan to rabbits were evaluated as sustained-release vehicles for the delivery of theophylline. In-vitro release of theophylline from gels formed by warming xyloglucan sols (0.5, 1.0 and 1.5% w/w) to 37 degrees C followed root-time kinetics over a period of 4 h. Gels formed after oral administration to rabbits of chilled 1.5% w/w aqueous solutions of xyloglucan containing dissolved drug showed sustained-release characteristics with a maximum plasma concentration at 4.5 h. The theophylline bioavailability from a 1.5% w/w xyloglucan gel was 1.7-2.5 times that of commercial oral sustained-release liquid dosage forms containing an identical theophylline concentration. It was concluded that dilute solutions of the enzyme-degraded xyloglucan had suitable rheological properties and in-situ gelling characteristics for use as sustained-release vehicles for oral drug delivery. The in-vivo release characteristics of theophylline in a rabbit model suggested the potential for the use of these vehicles in humans for the oral delivery of this drug.

In situ gelling xyloglucan formulations for sustained release ocular delivery of pilocarpine hydrochloride.

Thermoreversible gels formed in situ by aqueous solutions of an enzyme-degraded xyloglucan polysaccharide were evaluated as sustained release vehicles for the ocular delivery of pilocarpine hydrochloride. In vitro release of pilocarpine from gels formed by warming xyloglucan sols (1.0, 1.5 and 2.0% w/w) to 34 degrees C followed root-time kinetics over a period of 6 h. The miotic responses in rabbit following administration of xyloglucan sols were compared with those from in situ gelling Pluronic F127 sols and from an aqueous buffer solution containing the same drug concentration. Sustained release of pilocarpine was observed with all gels, the duration of miotic response increasing with increase of xyloglucan concentration. The degree of enhancement of miotic response following sustained release of pilocarpine from the 1.5% w/w xyloglucan gel was similar to that from a 25% w/w Pluronic F127 gel.

Trihalomethane removal by activated carbon fiber.

For the safety of drinking water, trihalomethanes are removed by adsorption onto activated carbon fiber from single-component solutions. The amounts adsorbed onto adsorbents with large surface area and/or pore volume were small. Stronger surface hydrophobicity of adsorbent was correlated with a larger amount of trihalomethanes adsorbed. A trihalomethane with bromine was adsorbed to a greater extent than that with chlorine. The differences in the amounts adsorbed among trihalomethanes can be explained by the polarity of trihalomethane molecules. The amount of trihalomethanes adsorbed was mainly dominated by the strength of hydrophobicity of activated carbon fibers.

Wistar strain rats as the model for IgE antibody experiments.

The amount of plasma IgE antibody formed and its change over time were investigated by enzyme-linked immunosorbent assay (ELISA) in male and female Sprague-Dawley (SD), Donryu, and Wistar strain rats. IgE antibody formation was initiated by injecting a mixture of 2,4-dinitrophenylated ascaris extract (DNP-As) as antigen and killed Bordetella pertussis as adjuvant into the paws of the animals. The amount of IgE antibody formed was low on day 10 in both male and female SD (40-80 ng/ml) and Donryu (20-40 ng/ml) strain rats, and an increase in the amount was observed on day 20. The peak value of IgE antibody was observed day 10 in Wistar strain rats and was 130 and 200 ng/ml in the male and female rats, respectively. These results suggest that Wistar strain rats produce the most IgE antibody when DNP-As is used as antigen and they can serve as a model for allergic diseases.