Differences in sperm motion between high- and low-shuttlebox avoidance rats (Hatano strains)

Sperm from the caudal epididymis of 2 inbred strains of Sprague-Dawley (SD) rats, selected on the basis of their high- or low-shuttlebox avoidance responses, were analyzed for motion characteristics by a computer-assisted sperm motion analysis (CASA) system. Sperm motion in high-avoidance animals (HAA) was characterized by high velocities, high amplitude of lateral head displacement (ALH), and low beat cross frequency (BCF). Conversely, sperm from low-avoidance animals (LAA) displayed low velocities, low ALH, and high BCF. These characteristics in sperm motion were not changed by washing. Furthermore, after treatment with alpha-chlorohydrin (aCH) as a male antifertility agent affecting rat epididymal sperm motion, sperm velocities in HAA rats were significantly reduced to levels similar to those in untreated LAA rats. However, ALH and BCF in HAA rats treated with aCH were different from those in untreated LAA rats. Sperm adenosine triphosphate (ATP) content was higher in HAA than in LAA rats, correlating with values of their sperm velocities. These data suggest there are apparent strain differences in sperm motion between HAA and LAA rats and that these differences are dependent on factors, including sperm energy production.     

Follow- up of coronary artery lesions caused by Kawasaki disease and the val ue of coronary angiography

目的：探讨川崎病后冠 状动脉病变及转归,以及二维超声心动图和选择性冠状动脉造影在冠状动脉病变判断和长期随访中的作用。方法：1979-1997年因川畸病在治疗和随访中发现有冠状动脉病变的87例,最长随访时间为16年6月。随访时给予阿斯匹林或阿斯匹林加华法令口服。每个病人每隔1-3年进行选择性冠状动脉及左室造影检查,直至正常。总共行选择性冠状动脉及左室造影167次,每次造影前均行二维超声心动图检查。结果：造影发现48/87（55％）病儿的冠状动脉病变在随访过程中消失,6/87（7％）病儿出现严重的冠状动脉病变导致明显的心肌缺血或心肌梗塞而需行冠状动脉搭桥手术。随着随访时间的延长,狭窄或血栓性冠状动脉病变的比例逐渐增高,冠状动脉瘤的比例逐渐降低。造影与二维超声心动图对照研究发现二维超声心动图检查存在假阳性和假阴性。二维超声心动图检查冠状动脉瘤的发现率为76％,狭窄或血栓性病变的发现率为18％,不能发现远端冠状动脉的狭窄或血栓性病变。结论：长期随访发现55％病儿的冠状动脉病变可以恢复正常,7％的病儿可发展成严重的冠状动脉病变。川崎病病儿均需长期随访,当出现严重冠状动脉病变时需及时处理。二维超声心动图检查不能替代选择性冠状动脉造影作川崎病后冠状动脉病变的长期随访。     

In vivo and in vitro evidence that cross-reactive antibodies to C-terminus of hypervariable region 1 do not neutralize heterologous hepatitis C virus

The hypervariable region 1 (HVR1) of hepatitis C virus (HCV) may contain neutralizing epitopes. A chimpanzee in whom cross-reactive anti-HVR1 antibodies had been induced by immunization was challenged with heterologous HCV for clarifying whether cross-reactive anti-HVR1 antibodies can neutralize heterologous HCV. Acute hepatitis C occurred in this chimpanzee after the challenge. Rechallenge with mixtures of the highest titer cross-reactive immune serum and heterologous HCV, after the chimpanzee had cleared the viremia, again resulted in HCV infection. Virus capture assay and inhibition of virus adsorption to susceptible cells, by the immune sera from the chimpanzee and highly cross-reactive monoclonal antibodies (mAbs) against the C-terminus of HVR1 of the challenge virus, showed that cross-reactive anti-HVR1 had no cross-neutralizing activity. The data imply that the HVR1 component is insufficient to develop an effective HCV vaccine.     

Dose-responsive alteration in hepatic lipid peroxidation and retinol metabolism with increasing dietary beta-carotene in iron deficient rats

Phosphatidylcholine hydroperoxide (PCOOH) levels are increased in the iron-deficient rat liver. We investigated the antioxidative effect of dietary beta-carotene and altered retinol metabolism in iron-deficient rats. Experiment 1: Male Wistar-strain rats were divided into six groups and fed a control diet, an iron-deficient diet, and iron-deficient diets with four different levels of dietary beta-carotene. The PCOOH concentration in the iron-deficient rat liver was decreased by supplementation with dietary beta-carotene. However, the beta-carotene dose response was not related to antioxidative potency. Hepatic and plasma beta-carotene concentrations were increased by iron deficiency. The hepatic retinol concentration was increased while the plasma retinol concentration was decreased in iron-deficient rats. Experiment 2: Male Wistar-strain rats were divided into two groups, with one group receiving a control diet with beta-carotene and the other an iron-deficient diet with beta-carotene. Intestinal iron was decreased and intestinal beta-carotene was unchanged in iron-deficient rats. The intestinal beta-carotene conversion ratio and beta-carotene cleavage enzyme activity were decreased in iron-deficient rats. Dietary beta-carotene played the role of an antioxidant in hepatic lipid peroxidation in the iron-deficient state, but there was no dose dependency. Moreover, intestinal beta-carotene cleavage and hepatic retinol release appear to be altered in iron-deficient rats.     

Targeting interleukin-4 receptors for effective pancreatic cancer therapy

We demonstrate that pancreatic cancer tissues express receptors for interleukin (IL)-4 in situ at high density. Using the approach of selective receptor targeting, we have tested the efficacy of a recombinant cytotoxin IL4-Pseudomonas exotoxin A, which is composed of a targeting moiety (IL-4) and a mutated form of Pseudomonas exotoxin. Our results demonstrate that this molecule exerts vigorous antitumor activity against human pancreatic tumors implanted s.c. in immunodeficient animals. Sixty percent of animals treated with intratumoral injections of IL4-Pseudomonas exotoxin A experienced complete disappearance of established tumors. Animals with pancreatic tumors implanted orthotopically exhibited prolonged survival that was significantly greater by comparison with untreated animals. Thus, IL-4 receptor-targeted cytotoxin represents a potent agent that may provide an effective therapy for pancreatic cancer.     

Expression of cell cycle control proteins in normal epithelium, premalignant and malignant lesions of oral cavity

In this study, we examined the expression of cyclins, cyclin dependent kinase (CDKs) and CDK inhibitors by immunohistochemical analysis in 20 normal mucosa, 42 epithelial dysplasia (ED), and 117 oral squamous cell carcinoma. Neither Cyclin D1 nor CDK2 were detectable in normal tissue and ED. Their presence, however, was detectable in squamous cell carcinoma (SCCs) (Cyclin D1, 35.9%; CDK2, 66.7%). Cyclin E was detectable in 57.1% of severe ED and 62.8% of SCCs. For the CDK inhibitors, these proteins were detectable in all normal mucosa and most of the mild and moderate ED. For severe ED, expression of these proteins was not observed in some cases (p12(DOC-1), 14.3%; p16(INK4A), 28.6%; p27(KIP1), 7.1%). For SCCs, the expression of p12(DOC-1) was lost in 71.8%, p16(INK4A) in 69.2% and p27(KIP1) in 35.9%. These results suggest that elevated expression of cyclin D1, cyclin E, CDK2 and loss of p12(DOC-1), p16(INK4A) and p27(KIP1) may contribute to the multistep nature of oral carcinogenesis.     

An antibody that binds to primary specific pocket-associated structure in the active site of bovine thrombin

We attempted to produce a monoclonal antibody (MAb) against the active site of native thrombin. Bovine thrombin was treated with diisopropyl fluorophosphate, and prepared diisopropylphosphoryl-thrombin was used for the immunization to BALB/c mice. Spleen cells of immunized mice were hybridized with mouse myeloma cells P3U1, and a hybridoma clone CC2, which produced a MAb against bovine thrombin was established. The MAb produced by hybridoma clone CC2 (MAb(CC2)), consisting of IgG(1) and kappa light chain, was purified using protein A affinity chromatography. Purified MAb(CC2) prolonged the fibrin forming time of bovine thrombin and inhibited the release of fibrinopeptide A from rabbit fibrinogen. In addition, it was found that argatroban partially, but competitively, interfere the binding between MAb(CC2) and bovine thrombin. It was then considered that MAb(CC2) would bind to the molecular structure associating primary specific pocket in the active site of bovine thrombin.     

Comparison of primary thyroid lymphoma with anaplastic thyroid carcinoma on computed tomographic imaging

PURPOSE: Primary non-Hodgkin's lymphoma (LY) and anaplastic carcinoma (AC) of the thyroid gland are rare malignant tumors, and the initial symptoms of these diseases are very similar. The aim of our study was to compare the characteristics of the two diseases using computed tomographic (CT) scans in order to make an accurate differential diagnosis. MATERIALS AND METHODS: Ten patients with LY and 10 with AC were analyzed. Differences in the CT findings of the two diseases were evaluated before treatment and statistically tested with either Student's t-test or the chi-square test. RESULTS: In the analysis of characteristics of CT imaging, the existence of calcification and necrosis, and heterogeneous tumor were dominant findings in AC, and there was a statistically significant difference in frequency between the two diseases (p < 0.01). Calcification detected in AC was usually multiple and/or gross (mean size: phi8.2 mm). All lymphadenopathies were delineated as having the same homogeneous attenuation as the tumors in the thyroid gland in LY, but were shown as irregular rim enhancement in AC. CONCLUSION: The CT features of the two diseases are characteristic in terms of calcification, necrosis, and tumor composition. Evaluation by means of CT imaging is useful in distinguishing between LY and AC.     

A network system of medical and welfare information service for the patients,their families,hospitals, local governments,and commercial companies in a medical service area

A service information system using the Internet, which connected the various people who are related to medical treatment and nursing welfare, was constructed. An intractable neurological disease patient who lives in the Onga district, Fukuoka, Japan, and the people who are related to the service were chosen as test users in an experimental model. The communicated service information was divided into open-use data (electronic bulletin board, welfare service, medical care service, and link to private company service home page) and closed-use data (the individual patient's hysterics). The open data server was installed in an Internet service provider The open data could be accessed not only by the patient, but also by the family, information center, companies, hospitals, and nursing commodity store related to patient's nursing and medical treatment. Closed data server was installed in an information center (public health center). Only patient and information center staff can access the closed data. Patients should search and collect the service information of various medical and welfare services by themselves. Therefore, services prepared for the patient are difficult to know, and they cannot be sufficiently utilized. With the use of this information system, all usable service information became accessible, and patients could easily use it. The electronic bulletin board system (BBS) was used by patients for knowing each other or each others' family, and was used as a device for exchange of wisdom. Also, the questions for the specialist, such as doctor, dentist, teacher, physical therapist, care manager, welfare office staff member, and public health nurse, and the answers were shown on the BBS. By arranging data file, a reference of various patients in question and answer, which appeared in this BBS, was made as "advisory hints" and was added to the open data. The advisory hints became the new service information for the patients and their family. This BBS discovered the possibility of becoming an important information source for companies, hospital and, administration to know the requirements of patients and their families and the kind of services to be served. Although suppliers provide medical and welfare services for the patient, there is a tendency that the service information is sent by the suppliers at their own convenience. The information system in which various people participated was constructed in order to collect information for the patient, taking a patient-oriented approach. The result of the model test showed that this information system using Internet technology is a good system for both the service supplier and its receiver.     

Paclitaxel and carboplatin combination chemotherapy in a hemodialysis patient with advanced ovarian cancer.

BACKGROUND: There are few reports on the pharmacokinetics of paclitaxel combined with carboplatin or on the dose schedule of carboplatin in combination use during hemodialysis in patients with ovarian cancer. CASE: A 40-year-old woman with chronic renal failure on hemodialysis who had FIGO stage III ovarian cancer was treated with debulking surgery and carboplatin/paclitaxel combination chemotherapy. Paclitaxal was administered at 150 mg/m(2) as a 3-h intravenous infusion followed by a 30-min infusion of carboplatin on a nondialysis day. The carboplatin dose was chosen to produce a target area under the concentration/time curve (AUC) of 5.0 microg-min/ml according to the Calvert formula. The pharmacokinetic study showed that the AUCs of free platinum and paclitaxel were 4.43 microg-min/ml and 15.9 microg-h/ml, respectively. Dosing of carboplatin based on the AUC produced an acceptable degree of thrombocytopenia and neutropenia. After the completion of five cycles of the combination chemotherapy, the tumor showed complete response, and the patient remained disease free for 8 months. CONCLUSION: Paclitaxel and carboplatin combination chemotherapy can be given to patients undergoing hemodialysis, with dialysis performed 16 h after the administration and with a dose adjustment of carboplatin to reach a target AUC. In these conditions, tumor response can be obtained.