Search

A male Drosophila that is not successful in courtship will reduce his courtship efforts in the next encounter with a female. This courtship suppression persists for more than 1 h in wild-type males. The Btk29A(ficP) mutant males null for the Btk29A type 2 isoform, a fly homolog of the nonreceptor tyrosine kinase Btk, show no courtship suppression, while Btk29A hypomorphic males exhibit a rapid decline in courtship suppression, leading to its complete loss within 30 min. The males of a revertant stock or Btk29A(ficP) males that are also mutant for parkas, a gene encoding the presumptive negative regulator of Btk29A, exhibit normal courtship suppression. Since another behavioral assay has shown that Btk29A(ficP) mutants are sensitization-defective, we hypothesize that the mutant flies are unable to maintain the neural excitation state acquired by experience, resulting in the rapid loss of courtship suppression., (© 2016 Wiley Periodicals, Inc.)

Spherical carbonate apatite (CO3Ap) microspheres approximately 1 mm in diameter were fabricated by granulation of calcium hydroxide around a core followed by carbonation and phosphatization through dissolution-precipitation reaction. CO3Ap microspheres with high uniformity could not be achieved without using a core. Solid CO3Ap microspheres were obtained using a calcite core whereas hollow CO3Ap microspheres were obtained using a NaCl core. The obtained microsphere was identified as B-type CO3Ap by Fourier transform infrared analysis and the carbonate content was approximately 7-8 wt% regardless of the type of core used for sample preparation. The mechanical strength of both the solid and hollow CO3Ap microspheres was sufficient for practical use as a bone substitute.

Objective: To investigate whether maximal sterile barrier precautions (MSBPs) during central venous catheter (CVC) insertion are truly effective in preventing catheter-related bloodstream infections (CRBSIs) in patients in general surgical units., Summary Background Data: The reported effectiveness of MSBPs was based on the results of a single-center randomized controlled trial by Raad et al and the majority of the patients (99%) in the study were chemotherapy outpatients., Methods: Between March 14, 2004 and December 28, 2006, the patients scheduled for CVC insertion in surgical units at 9 medical centers in Japan were randomly assigned to either an MSBP group (n = 211) or a standard sterile barrier precaution (SSBP) group (n = 213). This study was registered in the UMIN Clinical Trials Registry (registration ID number: UMIN000001400)., Results: The median (range) duration of catheterization was 14 days (0-92 days) in the MSBP group and 14 days (0-112 days) in the SSBP group. There were 5 cases (2.4%) of CRBSI in the MSBP group and 6 cases (2.8%) in the SSBP group (relative risk, 0.84; 95% confidence interval, 0.26-2.7; P = 0.77). The rate of CRBSIs per 1000 catheter days was 1.5 in the MSBP group and 1.6 in the SSBP group. There were 8 cases (3.8%) of catheter-related infections in the MSBP group and 7 cases (3.3%) in the SSBP group (relative risk, 1.2; 95% confidence interval, 0.43-3.1; P = 0.78). The rate of catheter-related infection per 1000 catheter days was 2.4 in the MSBP group and 1.9 in the SSBP group., Conclusions: This study is larger in sample size than the one performed by Raad et al and could not demonstrate better prevention of CRBSIs by MSBP compared with SSBP. A large randomized controlled trial or at least a meta-analysis of any other studies in the literature is necessary to reach to a conclusion on this issue.

Background/aims: This study aimed to measure hepatic blood flow increase in cases with liver metastasis and to diagnose minimal metastasis which cannot be visualized by imaging modalities., Methodology: The evaluation of hepatic arterial flow increase was performed quantitatively by newly devised index ELR (early-late-ratio) using dynamic computed tomographic (CT) scanning with contrast media., Results: The ratio of the cases with liver metastasis was significantly higher than that of normal liver control. It was revealed that the ratio was correlated with microvessel proliferation in the liver around the metastasis by examination of surgical specimen. Moreover, the patent group which proved to have metastasis within 6 months also had a significant higher ELR value., Conclusions: ELR not only was useful to evaluate hepatic blood flow increase in the cases with liver metastasis but also could be applied to predict the patent group with micrometastasis.

Breast cancer metastasis to pancreas is rarely seen. There have been only 6 cases described in the literature. We present the seventh case of a 54-year-old woman with breast cancer that metastasized to the tail of the pancreas 4 years and 4 months after radical mastectomy. Although the serum levels of CA15-3 and TPA had gradually increased without symptoms, it was difficult to establish the diagnosis before contrast-enhanced abdominal CT scan was performed. Immunohistochemical staining using E-cadherin was positive, proving that the breast cancer was ductal rather than lobular in origin. CA15-3 immunohistochemically stained positive in the resected pancreas lesion. Positive monoclonal staining by GCDFP-15 (gross cystic disease fluid protein-15) in the pancreas tumor also confirmed it breast cancer origin. Investigation of chemokine/chemokine receptors may clarify a new mechanism of metastasis to the pancreas from breast cancer.

The prognosis of patients with alpha-fetoprotein (AFP)-producing pancreatic cancer is generally very poor. We, however, present a case of a 33-year-old man who survived AFP-producing pancreatic cancer and its metachronous liver metastasis. The patient had undergone a curative total pancreatectomy for AFP-producing pancreas head cancer invading to the tail, which was postoperatively confirmed by immunohistochemical staining of the resected specimen. At 1 year and 4 months after the operation, the serum AFP level was elevated to 26 ng/mL, and a 2.6 cm-sized mass was found in the lateral segment of the liver. He underwent lateral segmentectomy, and the tumor was histopathologically diagnosed as having metastasized from the AFP-producing pancreatic cancer removed earlier. The patient is doing well 8 years and 5 months after resecting the liver metastasis, with no signs of recurrence. This case suggests that surgery may also be a treatment of choice for patients with liver metastasis from AFP-producing pancreatic cancer, particularly for those with a metachronous and solitary tumor. It should be remembered that some pancreatic cancers produce AFP and that monitoring of postoperative serum AFP levels in such cases will be useful for early detection of recurrence and selection of appropriate surgical intervention.

The aim of this study was to assess the face validity and practical utility of the Preoperative Assessment of Cancer in the Elderly (PACE) tool in a sample of elderly patients with cancer. A prospective series of such patients with breast, colorectal, upper gastrointestinal, and other cancers were interviewed using the PACE; patients were scored for presurgical assessment using standard measures, including American Society of Anesthesiologists physical status, the Physiological and Operative Severity Score for Enumeration of Mortality and Morbidity (POSSUM), the Portsmouth POSSUM, and World Health Organization performance status before undergoing standard surgical management. Short-term surgical outcome (in terms of mortality and morbidity) and cancer site-specific data were collected to identify the risk groups. Seventy-two patients took part in the study (participation rate of 97%). The interview in which the questionnaire was given was found to take 20 minutes on average. Face validity was demonstrated, with clear comprehension of the requirements of the PACE being shown by all patients. The 2 groups identified according to the presence (n = 24) or absence (n = 48) of postoperative mortality/morbidity were compared according to components of the PACE. The study identified possible associations between these components and postoperative morbidity. No postoperative mortality was recorded; however, 24 patients (33%) had surgical complications. Performance status and Activities of Daily Living classification were found to be significantly related to postoperative short-term morbidity, whereas a lower score on the Mini Mental State Examination and a higher score on the Geriatric Depression Scale were found to be related to postoperative morbidity, although they did not achieve statistical significance because of the small numbers involved. The authors have demonstrated the practicality and face validity of PACE and identified some associations with postoperative morbidity. Based on the findings of this pilot study, a large, international multicenter trial is planned.

Purpose: This study was designed to determine the clinical impact of carcinoembryonic antigen messenger ribonucleic acid expression in tumor-draining vein blood on postoperative liver metastasis in patients with colorectal carcinoma., Methods: The study comprised 37 patients with colorectal carcinoma who underwent laparotomy (Dukes A, 3; Dukes B, 16; Dukes C, 15; and Dukes D, 3). Blood samples were drawn from the tumor-draining vein and the tumor-feeding artery. Total ribonucleic acid was extracted from the blood and subjected to reverse transcriptase-polymerase chain reaction to detect carcinoembryonic antigen messenger ribonucleic acid. Tissue sections of tumor were stained with hematoxylin and eosin and were examined immunohistochemically. The duration of follow-up ranged from two years and three months to three years and six months., Results: Expression of amplified carcinoembryonic antigen messenger ribonucleic acid in tumor-draining vein blood was positive in 16 (43 percent) of the 37 patients, while that in the feeding artery blood was positive in 3 patients (8 percent). There was no relation between the protein level of carcinoembryonic antigen and positive expression of carcinoembryonic antigen messenger ribonucleic acid. Positive expression of carcinoembryonic antigen messenger ribonucleic acid was observed in two patients with histologic evidence of massive venous invasion and in all three patients with synchronous liver metastasis. Immunohistochemical studies revealed that all tumor specimens with stromal type (5/5) of carcinoembryonic antigen staining had positive expression of carcinoembryonic antigen messenger ribonucleic acid. Postoperative liver metastasis was detected in four patients, three of whom (75 percent) had positive expression of carcinoembryonic antigen messenger ribonucleic acid in tumor-draining vein blood., Conclusions: Positive expression of carcinoembryonic antigen messenger ribonucleic acid in tumor-draining vein blood differed by the type of immunohistochemical staining with carcinoembryonic antigen. These data suggest that patients with positive expression of carcinoembryonic antigen messenger ribonucleic acid in tumor-draining vein blood may be at a high risk for postoperative liver metastasis.

Background: Extended lymphadenectomy including lateral node dissection (EXT-L) contributes to a low incidence of local recurrence of lower rectal cancer. However, EXT-L is frequently associated with impairment of sexual and urinary function. We therefore compared the effectiveness of preoperative radiotherapy with that of EXT-L., Methods: One hundred fifteen patients were studied. Seventy-eight patients underwent preoperative radiotherapy with a total dose of 50 Gy (Rad[+] group), and 37 did not (Rad[-] group). Seventy-five patients received EXT-L (EXT-L[+] group), and 40 did not (EXT-L[-] group). Patients were further divided into 4 subgroups (Rad[+]&EXT-L[-], Rad(+)&EXT-L[+], Rad[-]&EXT-L(+), and Rad[-]&EXT-L[-]), and clinicopathologic features were examined. In the Rad(+) group, the relation between the p53 gene and survival was also examined., Results: There was a significant difference in disease-free survival between the Rad(+) and Rad(-) groups (5-year disease-free survival rate, 74.6% vs 45.9%; P =.006). However, there was no significant difference between the Rad(+)&EXT-L[-] and Rad[-]&EXT-L(+) groups. The p53 gene status did not affect survival in the Rad(+) group., Conclusions: This study suggests that in terms of curative effect, preoperative radiotherapy can be one alternative therapy in place of EXT-L for patients with lower rectal cancer.

The results of a questionnaire survey conducted by the Colorectal Surgical Club were analyzed to elucidate how clinical trials performed as well as points of concern in the treatment of colorectal cancer by colorectal specialists in Japan. Of the specialists, 92.2% responded that systemic chemotherapy was necessary for curA (Dukes C), in almost all cases administered postoperatively either orally or intravenously, and 96.6% said systemic chemotherapy was necessary for unresectable colorectal cancer, in almost all cases administered intravenously in combinations of anticancer drugs. The things considered most important for systemic chemotherapy were survival rate, effective rate, and safety, while the most for which most care was taken were patient consultations, periodical blood examination, and observance of drug application and dosage.

Purpose: The effectiveness of preoperative radiation therapy for advanced lower rectal carcinoma to preserve the function of pelvic organs and reduce local recurrences was examined in a prospective, randomized, controlled study., Methods: Fifty-one patients with a diagnosis of localized and resectable adenocarcinoma of the lower rectum undergoing 50 Gy of preoperative radiotherapy were recruited into the trial between April 1993 and March 1995. The patients were randomly allocated to complete autonomic nerve-preserving surgery without lateral node dissection (D1), or surgery with dissection of the lateral lymph nodes including autonomic nerves (D2) followed by oral administration of carmofur for one year., Results: No difference was observed in either survival or disease-free survival between D1 and D2 groups. There was no difference between the two groups in terms of recurrence rate. A significant difference was observed in urinary and sexual function (P = 0.02 and 0.02, respectively) one year after surgery between D1 and D2 groups., Conclusion: This study suggests that lateral node dissection is not necessary in terms of curability for patients with advanced carcinoma of the lower rectum who undergo preoperative radiotherapy.

Purpose: The aim of this study was to determine how extensive resection affects operative morbidity, mortality, and long-term survival in elderly patients with colorectal cancer., Methods: A total of 119 patients 80 years of age or older were given a diagnosis of colorectal carcinoma at our hospital between 1985 and 1997. Eleven patients who did not undergo surgery were excluded. The remaining 108 patients underwent laparotomy and were reviewed. Serum levels of interleukin-6 were measured perioperatively in 22 patients to assess the degree of operative stress., Results: Potentially curative resection was performed in 64 (88.9 percent) of the 72 patients in the active performance status group and 13 (36.1 percent) of the 36 patients in the sedentary performance status group (P < 0.001). The in-hospital mortality rate was 8.3 percent in group the active performance status group and 38 percent in the sedentary performance status group (P = 0.007). Patients in the sedentary performance status group and those who underwent emergency operations had higher levels of IL-6 than patients in the active performance status group or those who underwent elective operations., Conclusions: Preoperative performance status, operative curability, and tumor stage have a significant impact on outcome in patients with colorectal cancer who are 80 years of age or older. Knowledge of early postoperative response of IL-6 is useful in predicting postoperative mortality and morbidity in this subgroup of patients.

Purpose: The accuracy of diagnosis of metastatic lymph nodes for rectal carcinoma has not improved. A low echoic lesion more than 5 mm in size detected by endorectal ultrasonography is preoperatively assessed as a metastatic lymph node. What does a low echoic lesion more than 5 mm in size correspond to histologically?, Methods: Forty-seven patients with lower rectal carcinoma (Term I, 1986-1990) and 48 patients with lower rectal carcinoma (Term II, 1991-1995) undergoing endorectal ultrasonography were reviewed. Surgically resected rectal specimens from 40 patients with rectal carcinoma underwent ultrasonography. Low echoic lesions more than 5 mm in size were taken from resected specimens and were stained with hematoxylin, followed by histologic examination., Results: The accuracy of diagnosis of metastatic lymph nodes of Term II was not higher than that of Term I. Twenty-five low echoic lesions were detected by ultrasonography using 40 resected specimens. Seventeen of these 25 lesions (68 percent) were histologically confirmed to be metastatic lymph nodes. One of 25 (4 percent) was found to be lymphadenitis with no metastasis. Among the 25 lesions, 5 (20 percent) were histologically confirmed to be tumor deposits, 2 (8 percent) fatty tissue, and 22 (88 percent) carcinoma., Conclusions: Low echoic lesions were histologically confirmed to be tumor deposits (20 percent) and metastatic lymph nodes (68 percent). Although these data show deficiencies and limitations of the accuracy of endorectal ultrasonography, they compare favorably with other series, and no other current technology can show similar accuracy.

Purpose: We observed small spots at the margin of rectal carcinomas on endorectal ultrasonography. Our aim was to study the relationship between ultrasonographic evidence of these spots and histologic characteristics of disease and postoperative recurrence., Patients and Methods: The study group comprised 55 patients, 36 men and 19 women, with rectal carcinoma as confirmed by biopsy. The patients were followed up at three-month intervals for six months to three years and six months after the operation. Endorectal ultrasonography was performed in the usual manner. Surgically resected specimens were stained with hematoxylin and eosin and histologically examined. Vessel invasion was graded from 0 (not invasive) to 3 (most invasive)., Results: Among the 55 patients studied, 3 had Stage T2,N0,M0 rectal carcinomas and 35 had Stage T3,N0,M0 carcinomas, 5 (14.3 percent) of whom had echographic evidence of small spots. Thirteen patients had Stage T3,N1/2,M0 carcinomas, comprising 12 (92.3 percent) with small spots, and four patients had T3,N1/2,M1 carcinomas, all with small spots. Vessel invasion of Grade 2 or higher was observed around the carcinomas in 20 of 21 patients who had small spots. Ten of 13 patients with many spots at the margin of the carcinoma (a spot grade of ++) histologically had marked venous or lymphatic invasion (an invasion Grade 3). The presence of small spots was closely associated with massive venous or lymphatic invasion (a vessel invasion grade of 2 or more). Four patients had synchronous liver metastases, and small spots were found in all four. Distant metastases and local recurrence were found in 11 of 21 patients with small spots. We found no recurrence in any patient without small spots on endorectal ultrasonography., Conclusions: Small spots indicate the presence of massive venous or lymphatic invasion and a high risk of postoperative recurrence.

Purpose: To clarify the relation between tumor-suppressor gene p53 expression and histologic grades of dysplasia in colorectal adenomas, we performed immunohistochemical analysis in a series of 59 colorectal polyps and 40 advanced carcinomas., Methods: Adenomatous polyps were stained by hematoxylin and eosin and classified into mild, moderate, and severe dysplasia (intramucosal carcinoma), according to the World Health Organization's classification., Results: p53 was positive in 7.1 percent (2/28) of mild, 29.4 percent (5/17) of moderate, and 62.5 percent (5/8) of severe dysplasia. In submucosal and advanced carcinomas, positivity rates were 75 percent (3/4) and 47.5 percent (19/40), respectively. Different staining patterns were found, according to grades of dysplasia. In the adenomas with mild or moderate dysplasia, a few focal crypts showed localized p53-positive staining. Adenomas with severe dysplasia had two different staining types. One was a focal staining type as shown in mild or moderate dysplasia; the other was a diffuse staining type, in which glands with mild or moderate dysplasia, surrounding severe dysplasia area, were also stained. Submucosal and advanced carcinomas showed a strong positive staining in cancer cells only., Conclusions: Overexpression of p53 protein in adenomas with mild or moderate dysplasia and existence of two types of expression in adenomas with severe dysplasia were observed. These facts suggested the possible existence of different pathways in the adenoma to carcinoma progression.

Endoscopic polypectomy should be applied only for early colorectal carcinomas. Intramucosal carcinoma do not have a risk of lymph node metastases. However, there is an about 10% risk of lymph node metastases among carcinomas showing submucosal invasion (sm carcinoma). When risk factors revealed to be positive after polypectomy, subsequent surgical resection of the large bowel with lymph nodes dissection is needed, because these sm carcinomas are considered to have a high risk of lymph node metastases. Therefore, accurate diagnosis of depth of invasion is essential to prevent subsequent surgical resection following endoscopic polypectomy. Endoscopy, barium enema and endoscopic ultrasonography (EUS) are all considered to be effective for an accurate diagnosis of depth of invasion. Endoscopic polypectomy includes hot biopsy, snare polypectomy and endoscopic mucosal resection (EMR). Appropriate maneuver must be chosen, considering the characteristics of the lesion. Major complications after endoscopic polypectomy are bleeding and perforation of the large bowel. Including an establishment of a new risk factors, further efforts must be made to prevent unnecessary additional surgical resection of the large bowel following endoscopic polypectomy.

The purpose of this study is to demonstrate the applicability of DNA ploidy analysis by using touch preparations obtained from fresh and frozen tissues on the prognostic evaluations of colorectal cancer, especially the development of hepatic metastases. The specimens obtained from surgically resected colorectal carcinomas (32), and hepatic metastases (4), were lightly touched with the slide glasses. Among the 32 patients with colorectal cancers, 7 had synchronous liver metastases, and 5 metastases developed metachronously. After formalin-fixation and Feulgen staining, the DNA analysis was performed by image cytometer (ICM, CAS200R). The data were expressed as the ploidy patterns and DNA indices (p-DNAI: peak DNA index, m-DNAI: mean DNA index), and were correlated very well with those obtained from cytophotometry. The DNA ploidy pattern among the 32 colorectal cancer specimens were Aneuploid(A) in 16, Polyploid (P) in 7, Diploid (D) in 4 and D+P in 5. The cases with synchronous or metachronous liver metastases had a higher m-DNAI (1.74 +/- 0.28) and were Aneuploid in 8, P in 3, and D+P in 1 case. Aneuploidy or Polyploidy predominated among the cases with metachronous liver metastases (4 in 5 cases), with m-DNAI higher than 1.5. Thus, "m-DNA > 1.5" could be a useful prognostic indicator of the high risk group of liver metastases. The liver metastases specimens had Aneuploid and Polyploid patterns in 2 cases each, with m-DNAI ranging from 1.88 to 2.31. DNA ploidy pattern analysis using touch preparations with image cytometry may be useful in determining the prognosis for colorectal cancer.

Because leukocyte-mediated tissue damage is an important component of the pathologic picture in ischemia/reperfusion, we have sought mechanisms by which PMNs are directed into hypoxic tissue. Incubation of human endothelial cells (ECs) in hypoxia, PO2 approximately 14-18 Torr, led to time-dependent release of IL-8 antigen into the conditioned medium; this was accompanied by increased chemotactic activity for PMNs, blocked by antibody to IL-8. Production of IL-8 by hypoxic ECs occurred concomitantly with both increased levels of IL-8 mRNA, based on polymerase chain reaction analysis, and increased IL-8 transcription, based on nuclear run-on assays. Northern analysis of mRNA from hypoxic ECs also demonstrated increased levels of mRNA for macrophage chemotactic protein-1, another member of the chemokine superfamily of proinflammatory cytokines. IL-8 gene induction was associated with the presence of increased binding activity in nuclear extracts from hypoxic ECs for the NF-kB site. Studies with human umbilical vein segments exposed to hypoxia also demonstrated increased elaboration of IL-8 antigen compared with normoxic controls. In mice exposed to hypoxia (PO2 approximately 30-40 Torr), there was increased pulmonary leukostasis, as evidenced by increased myeloperoxidase activity in tissue homogenates. In parallel, increased levels of transcripts for IP-10, a murine homologue in the chemokine family related to IL-8, were observed in hypoxic lung tissue. Taken together, these data suggest that hypoxia constitutes a stimulus for leukocyte chemotaxis and tissue leukostasis.

We examined six mouse strains, A/J, DBA/2, WBB6F1-W/Wv, WBB6F1- +/+, C3H/HeN, C57BL/6, for their bronchial reactivity to methacholine and serotonin. The mice were anaesthetized with intraperitoneal sodium pentobarbital. The trachea was intubated and one jugular vein was cannulated. Then, the mice were ventilated on air, using a small animal ventilator at a rate of 60 strokes/min with a tidal volume of 0.5 ml. Methacholine and serotonin diluted to various concentrations were administered intravenously. Bronchoconstriction was assessed by the modified Konzett-Rossler method. According to their bronchial responsiveness to methacholine and serotonin, the strains were grouped into high- (A/J, DBA/2), middle- (WBB6F1-W/Wv, -+/+) or low- (C3H/HeN, C57BL/6) responder groups.

The subsets of tumor-infiltrating lymphocytes (TIL) and prostaglandin (PG) E2 were measured in the resected tissues of 32 colorectal cancers without metastasis and 14 with metastasis in order to investigate the local immunity in metastasis of colorectal carcinoma. Subsets of TIL (Leu 1, Leu 2a, Leu 3a, Leu 10, Leu 11b, IL-2 receptor) were detected by immunohistochemical staining of frozen tissues. The number of positive cells was counted and expressed as number positive per 250 x 250 microns 2. The numbers of T cells (Leu 1) and natural killer cells (Leu 11b) were larger in early cancers and decreased in parallel with the presence of metastasis (control [n = 9]: 89 +/- 28, 6 +/- 4; early cancers [n = 9]: 269 +/- 112*, 76 +/- 56*; advanced cancers without metastasis [n = 11]: 182 +/- 80*, 56 +/- 59*; advanced cancers with metastasis [n = 11]: 76 +/- 42*, 26 +/- 21; values are mean +/- SD; * P less than 0.05, ANOVA). The level of PG E2 from the draining vein (V) measured by radioimmunoassay was higher than that from the feeding artery (A) (119.1 +/- 14.3 vs. 15.4 +/- 1.9 pg/ml; P less than 0.001). The PG E2 V/A ratio of cancers with metastasis was significantly higher than that of those without metastasis (13.2 +/- 2.4 vs. 5.6 +/- 0.8; P less than 0.001). TIL was decreased in parallel with the increase of PG E2 V/A ratio. We conclude that TIL and PG E2 may play an important role in metastasis of colorectal carcinoma and that PG E2 has an adverse effect in suppressing local immunity and enhancing metastasis.

In eight subjects who showed dual asthmatic response (DAR) in bronchial provocation tests (BPT) with specific allergens, local allergen challenge (LAC) was conducted using a flexible bronchofiberscope. We examined the concentrations of histamine, leukotriene B4 and C4 (LTB4 and LTC4) and cell populations in bronchoalveolar lavage fluid (BALF) collected before LAC (control), during the immediate response phase (IR), and the late response phase (LR). Control BALF was collected from the left lingula (B4 or B5), and BALF in the IR or LR phase from the right middle lobe (B4 or B5). Each BAL was conducted with 50 ml of saline at 37 degrees C and repeated three times in succession. It was noted that histamine increased significantly (p less than 0.05) in IR-BALF from the control level. In addition, the concentrations of LTC4 and the numbers of eosinophils increased in IR-BALF. In LR-BALF, the numbers of eosinophils (p less than 0.01), and the concentrations of histamine (p less than 0.05), LTC4 (p less than 0.05) and LTB4 increased. From these results, it was suggested that infiltration of eosinophils and various chemical mediators in the bronchial mucosa play important roles in the development of late asthmatic response.

We have previously demonstrated that airway responsiveness was enhanced following a late bronchial response (LBR) after an allergen challenge in ovalbumin (OA)-sensitized guinea pigs. The purpose of the present studies was to evaluate whether airway responsiveness to methacholine increased after an immediate bronchial response (IBR) and the possible involvement of the beta-adrenoceptor dysfunction in OA-sensitized guinea pigs. Guinea pigs were actively sensitized by aerosolized OA. Following OA exposure, IBR appeared. After IBR when specific airway resistance returned to the base line value, airway responsiveness to methacholine increased significantly. Before OA exposure, propranolol induced bronchoconstriction (PIB) was not provoked, however, after IBR, PIB was provoked and the guinea pigs died because of severe bronchoconstriction. These results suggest that airway responsiveness to methacholine increases significantly after IBR. Furthermore, the dysfunction of the beta-adrenoceptor may be a mechanism of this hyperresponsiveness in OA-sensitized guinea pigs.

We studied the time related changes of airway hyperresponsiveness induced by ozone inhalation (2.9 ppm, 30 min) in guinea pigs. In unanesthetized and spontaneously breathing guinea pigs, the respiratory resistance was measured by a forced oscillation technique. The respiratory resistance and respiratory frequency were unchanged until 24 hours after ozone inhalation. In mechanically ventilated guinea pigs, airway responsiveness to inhaled methacholine was determined using a modification of the Konzett-Rössler technique, and after methacholine challenge bronchoalveolar lavage (BAL) was performed for cell yield. At 1 hour and 3 hours after ozone inhalation, airway responsiveness was increased significantly, but returned to the control level at 6 hours. In the BAL fluid, there was a significant increase in neutrophils at 3 hours after ozone inhalation and thereafter. In the separated groups, before air or ozone inhalation, human serum albumin (HSA) was administered intravenously, and BAL was performed 1 hour after inhalation. In the ozone inhalation group, the concentration of HSA in BALF was increased significantly compared to the air inhalation group. These results suggest that airway hyperresponsiveness induced by ozone inhalation may occur before the influx of neutrophils into the airways and may depend on some structural changes such as submucosal and mucosal edema induced by the enhancement of capillary permeability.