The EKER rat, a model of dominantly inherited cancer syndrome.
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Biomedical subjects
Publications and source records attributed to Y Kikuchi.
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Antiestrogens (AEs) have been considered to elicit antitumor effects via estrogen receptor. However, recent reports have demonstrated that AEs had an antitumor effect even in cases without estrogen receptor, and that AEs caused various kinds of biological behavior such as a chemosensitizing effect. We therefore investigated the possibility of circumvention of cisplatin (CDDP) resistance due to the chemosensitizing effect of AEs by using 5 ovarian cancer cell lines. They were named KF, MH, KK, KFra and KFrb cell lines. KF and MH were derived from serous cystadenocarcinomas, and KK from a clear cell carcinoma. KFra and KFrb were CDDP-resistant cell lines developed from the KF cell line. MCF-7 cell line derived from breast cancer was used as a control. The study of a 50% inhibitory concentration (IC50) revealed that clomiphene (CLO) had the most potent antiproliferative effect among the AEs used, and was followed by tamoxifen (TAM) and toremifene (TOR) with a similar effect. On the whole, the degree of CDDP sensitivity was not correlated with the degree of AE sensitivity. KFra cell line which had the highest CDDP-resistance among the 5 ovarian cancer cell lines used was the most sensitive to AEs, especially to CLO. In the study on the combined administration of CDDP and AEs, 1 microM of CLO significantly reduced the IC50 of CDDP to KFrb, KK and MCF-7 cell lines. Similarly, 1 microM of TAM significantly reduced the IC50 of CDDP to KF, KFra and MCF-7 cell lines, and 1 microM of TOR significantly reduced it to KFra, KK and MCF-7 cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)
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The combination of radiotherapy and thermotherapy has the greatest antitumor effect when delivered simultaneously. We developed and have clinically used an applicator that enables simultaneous intraluminal irradiation and hyperthermia delivery for the treatment of locally invasive esophageal carcinoma. In a phase 1 study, 40 Gy of external irradiation was delivered followed by simultaneous intraluminal hyperthermia and radiotherapy once weekly for three weeks. Intraluminal hyperthermia was delivered to the mucosal surface at 42 to 44 degrees C for 30 minutes. Intraluminal irradiation (3 Gy) was delivered to a submucosal depth of 5 mm after the first 15 minutes of hyperthermia. This treatment may increase current treatment results for locally invasive esophageal carcinoma, which have otherwise been maximized.
We report three cases in which continuous intra-arterial infusion therapy via the occipital artery was combined with radiotherapy for head and neck tumors. An angiographic catheter was inserted into the feeding artery of the tumor retrogradely via the occipital artery under fluoroscopic guidance. Patients treated were maxillary sinus cancer, tongue cancer and hemangiosarcoma. No complications occurred due to this procedure in any of the three patients. This procedure was considered very useful when the approach from the superficial temporal artery was not possible due to prior treatment.
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The respiratory tract epithelium in many vertebrate species has a neuroepithelial endocrine (NEE) system. This system is composed of solitary NEE cells or organoid cell groups called neuroepithelial bodies (NEBs). In response to chemical and physical stimuli, NEE cells may release bioactive substances. Serotonin, one of the biogenic amines, well-known as a constricter of smooth muscle, can be found in NEE cells, serotonin-immunoreactive cells can be used as a marker for these cells. Comparative histological studies of lower vertebrates can improve our understanding of mammalian respiratory systems. The Tokyo salamander (Hynobius neblosus tokyoensis Tago), classified as Ulodera, is particularly useful for comparative studies of respiration. In this study, the serial sections of respiratory tract of the Tokyo salamander were stained by a commonly used staining method and by an immunocytochemical method for serotonin, and the distribution of serotonin-immunoreactive cells in the respiratory tract was examined. The respiratory tract was found to be connected to the alimentary tract via an aditus laryngis, which opens on the medio-ventral side of the esophagus. The laryngotrachea was slit-like or elliptically shaped with a total length of about 3.5 mm, joining the aditus laryngis. The laryngotrachea was supported by a pair of lateral cartilages, and a fibromuscular layer was seen between the cartilages and the epithelium. In the cranial region, a laryngeal sphincter was seen around the laryngotrachea. The laryngotrachea branches into a pair of tube-like lungs, that are about 17-20 mm in length. Two apposed primary trabeclae run along the entire length of the lung wall, perpendicular to the axis, and containing the pulmonary arteries and veins. The lungs were divided into two portions: 1) an airway portion (trabeclae, septa) in which smooth muscles surrounding the large vessels were well developed, and 2) a respiratory portion which was give that name because it has well developed capillary networks that were assumed to be involved in gas exchange. The lumen of the laryngotrachea and the pulmonary airway portion contained pseudostratified cilio-mucous epithelium. In the caudaldorsal region of the laryngotrachea adjacent to the lungs, the non-ciliated respiratory epithelium was seen lining the capillaries. In cilio-mucous epithelium of the laryngotrachea, all serotonin-immunoreactive cells were solitary. They apposed to be columnar, cuboidal, triangular, oval, and flask- or spindle-shaped. Solitary serotonin-immunoreactive cells were classified "open type cell" with appical process reaching to the luminal surface and "closed type cell" insulated from the lumen by an epithelial lining. In the pulmonary airway portion, serotonin-immunoreactive cells were solitary cells and in clusters. Serotonin-immunoreactive cells were widely distributed throughout the respiratory tract, but they tended to be found mainly in the cranial portion. The density was highest in the area with the laryngeal sphincter, and decreased caudally in the laryngotrachea and lung. No serotonin-immunoreactive cells were found in the respiratory portion of the dorsal-caudal area of the laryngotrachea or in the part of the lung with non-ciliated cells. So the structure and distribution of serotonin-immunoreactive cells in the respiratory tract of the Tokyo salamander are similar to those of NEE cells and NEBs in mammalian respiratory systems. The density of serotonin-immunoreactive cells appears to be related to the distribution of smooth muscles in the fibromuscular layer and airway portion. The cells may be involved in regulation of the respiratory system. Serotonin is released in response to stimulation, which could result in constriction of the fibromuscular layer and shrinkage of the laryngotracheal cavity, and may regulate pulmonary volume by constricting smooth muscles
Screening for sleep-disordered breathing is often done in an interview and with a questionnaire. This method is indirect and it appears to underestimate the prevalence of sleep apnea syndrome. Recently, several devices such as the Medilog and Vitalog portable monitoring systems were developed. However, these devices are difficult for patients to operate by themselves, because they include EEG monitoring or measurement of chest and abdominal movement. Therefore, we developed a portable monitoring system that is easier to operate. This system can be used to assess three variables: oronasal airflow, tracheal sound, and electrical activity of the heart. It stores the time of the onset of apnea, apnea duration, and R-R intervals with a built-in microcomputer. Apnea episodes, total apnea time, mean apnea time, and R-R interval are analyzed with a host computer. The sensitivity an specificity of this system are 92.5% and 87.5%, respectively, with an apnea index (AI) of less than 10 episodes/h. Using this device, we found that the prevalence of sleep apnea syndrome among Japanese industrial workers who had an AI of more than 10 episodes was 7.5%. Moreover, from 1984 to 1994 we used this device to monitor 1019 outpatients who complained of sleep disturbances such as snoring, abnormal breathing during sleep, and excessive daytime sleepiness, and found sleep apnea (AI > or = 10) in about 50% of these patients. This monitoring system is useful for screening of outpatients with sleep apnea and for epidemiological studies of sleep apnea. However, it may be necessary to include a non-invasive system for monitoring oxygen saturation in the portable sleep monitor, to detect hypoventilation during sleep.
We have previously shown that the hairpin ribozyme-like structure of the negative strand of the satellite RNA of arabis mosaic virus [(- )sArMV] has indeed ribozyme activity. However, some mutagenesis analyses revealed surprisingly that the wild type ribozyme was less active than almost all the other mutant ribozymes tested. These results were derived from a trans-acting system. Here we tested this ribozyme activity in a cis-acting system. We show that the (-)s ArMV hairpin ribozyme has different target-site specificities between cis and trans cleavages. The wild type ribozyme has the highest self-cleaving activity among the ribozyme variants tested.
This study clarifies the characteristics of the time keys that are taken to enter Roman letters for Japanese sentences. First, test the appearance frequency of two consecutive characters of the alphabet in the input of English sentences and in the input of the Roman characters of Japanese sentences. Based on these results, we analyzed the features of stroke frequency of the keys in the Roman character input. Based on the result of the analysis, we clarified the features of the keystroke interval time for two consecutive characters in the Roman character input. Then, keys were struck to enter Japanese sentences for a fixed period of time and a test was made for the characteristics. As a result, the following points were clarified: 1) The time keys struck were divided into two large groups. One for two consecutive alphabet letters that corresponded to Kana, or the Japanese syllabary, and the other with no correspondence. The former had smaller values for the mean time and deviations, and the latter had larger values for them. 2) The subjects who struck a larger number of keys per unit time took less time in typing two consecutive letters which did not correspond to Kana.
The purpose of the present study was to evaluate the muscular load of the arm when combing the hair using different "kuru-kuru" type of hair driers. Ten female students (20-24 years old) volunteered as subjects. Five combing patterns were conducted as follows: 1) comb outer layer of right side of hair using right hand, 2) comb outer layer of left side of hair using right hand, 3) comb inner layer of left side of hair using right hand, 4) comb outer layer of back hair using right hand, and 5) comb inner layer of right side of hair using left hand. Surface EMGs were recorded from M. flexor carpi ulnaris, M. brachioradialis, M. biceps brachii, M. triceps brachii, M. deltoideus and M. trapezius of both sides of body. Integrated EMGs (iEMGs) were used to evaluate muscular load for each of the seven different types of hair driers used. The relationship between iEMGs and weight, center of gravity, diameter, length, and circumference of each hair drier were examined. The weight of hair driers tended to be the effective factor on the muscular load. Muscular load also had a tendency to be affected by the shape of the grips. With regard to the hand size, the longer the thumb length, the smaller is the muscular load. It was suggested that a relatively large diameter of the bulb-shaped grip of the drier gave a smaller muscular load among the hair driers examined in the present experiment.
Interleukin 5 (IL-5) induces proliferation and differentiation of B cells and eosinophils by interacting with its receptor (IL-5R) which consists of two distinct polypeptide chains, alpha and beta (beta c). Although both IL-5R alpha and beta c lack a kinase catalytic domain, IL-5 is capable of inducing tyrosine phosphorylation of cellular proteins. We investigated the role of IL-5R alpha in tyrosine phosphorylation of molecules involved in IL-5 signal transduction, using an IL-5-dependent early B cell line, Y16 and transfectants expressing intact or mutant IL-5R alpha together with intact beta c. The results revealed that the transfectants expressing truncated IL-5R alpha, which entirely lacks a cytoplasmic domain, together with beta c, showed neither protein-tyrosine phosphorylation nor proliferation in response to IL-5. This confirms that IL-5R alpha plays a critical role in protein-tyrosine phosphorylation which triggers cell growth. IL-5 stimulation results in rapid tyrosine phosphorylation of beta c and proteins containing Src homology 2 (SH2) and/or SH3 domains such as phosphatidyl-inositol-3 kinase, Shc, Vav, and HS1, suggesting their involvement in IL-5-mediated signal transduction. IL-5 stimulation significantly enhanced activities of Janus 2 and B cell-specific Bruton's tyrosine kinases (JAK2 and Btk) and increased the tyrosine phosphorylation of JAK2 kinase. These results and recent data on signaling of growth factors taken together, multiple biochemical pathways driven by tyrosine kinases such as JAK2 and Btk are involved in IL-5 signal transduction.
A new temperature-sensitive mutant of Saccharomyces cerevisiae was isolated. Arrested cells grown at the nonpermissive temperature were of dumb-bell shape and contained large vacuoles. A DNA fragment was cloned based on its ability to complement this temperature sensitivity. The HTR1 gene encodes a putative protein of 93 kDa without significant homology to any known proteins. The gene was mapped between ade5 and lys5 on the left arm of chromosome VII. The phenotype of the gene disruptant appeared to be strain-specific; disruption of the gene in strain W303 caused the cells to become temperature sensitive. The arrested phenotype here was similar to that of the original ts mutant and cells in G2/M phase predominated at high temperature. Another disruptant in a strain YPH background grew slowly at high temperature due to slow progression through G2/M phase, and morphologically abnormal (elongated) cells accumulated. A single-copy suppressor that alleviated the temperature-sensitive defects in both strains was identified as MCS1/SSD1. The wild-type strains W303 and YPH are known to carry defective MCS1/SSD1 alleles; hence HTR1 may function redundantly with MCS1/SSD1 to suppress the temperature-sensitive phenotypes. In addition, based on a halo bioassay, the disruptant strains appeared to be defective in recovery from, or adaptive response to G1 arrest mediated by mating pheromone, even at the permissive temperature. Thus the gene has at least two functions and is designated HTR1 (required for high temperature growth and recovery from G1 arrest induced by mating pheromone).
The Eker rat is a promising animal model of cancer predisposition syndromes. In this study, using 129 backcross animals, we have established a new conserved linkage group on rat 10q and human 16p13.3 whereby the Eker mutation was found to be tightly linked to the tuberous sclerosis (TSC2) gene. This will be the first step toward the positional cloning and identification of the predisposing Eker mutation.
The nucleotide sequence of the upstream region of the bphC gene from Pseudomonas sp. strain KKS102 was determined. Four genes were found in this region. Deduced amino acid sequences of the first, second, third and fourth genes showed significant homology with a large subunit of iron-sulfur protein, a small subunit of iron-sulfur protein, ferredoxin and dihydrodiol dehydrogenase, respectively, from other bacteria which degrade biphenyl/polychlorinated biphenyls, toluene and benzene. E. coli, in which the four genes, bphC and the gene for ferredoxin reductase from benzene degrading bacterium were expressed, was able to produce meta-cleavage compounds from chlorinated biphenyls. These results show that these gene products are functional in both biphenyl and polychlorinated biphenyls degradation.
1. An attempt has been made to test the hypothesis that, in the caudal part of nucleus tractus solitarii (NTS) where carotid sinus nerve (CSN) afferents project, L-glutamate (Glut) modulates the hypoxic ventilatory response. 2. Unanaesthetized, peripherally chemodenervated (carotid body denervated; CBD) and sham-operated, freely moving rats were used. During peripheral chemoreceptor stimulation by hypoxia (10% O2 for 30 min) or doxapram (Dox) infusion (2 mg kg-1 (30 min)-1), ventilation was recorded and successively, under the same conditions, the extracellular Glut concentration ([Glut]o) in the caudal NTS was measured by in vivo microdialysis. [Glut]o was also measured during hyperoxic hypercapnia (10% CO2-30% O2 for 30 min). 3. Furthermore, the effects on ventilation of exogenous Glut, the NMDA (N-methyl-D-aspartate) receptor antagonist MK-801 or the ionotropic receptor antagonist kynurenate microinjected into the caudal NTS were investigated in sham-operated rats. 4. In sham-operated rats, both ventilation and [Glut]o in NTS were increased during peripheral chemoreceptor stimulation. On the other hand, no increases in either ventilation or Glut release were observed in CBD rats. In spite of ventilatory augmentation during hypercapnia, no response of [Glut]o to hypercapnia was observed in either group. 5. Local Glut application into NTS increased ventilation. Pretreatment with MK-801 or kynurenate reduced the hypoxic ventilatory response. This reduction in ventilation was mainly due to the decrease in tidal volume. 6. These results suggest that hypoxia induced the release of Glut in NTS and that this effect was mediated by arterial chemosensory input.