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Biomedical subjects

E Wada

Publications and source records attributed to E Wada.

At least 37 records · Page 2Linked to original sources
PubMed2000

Bombesin-like peptides: studies on food intake and social behaviour with receptor knock-out mice.

Bombesin (BN)-like peptides and receptors for these peptides are widely distributed in mammalian peripheral tissues and the central nervous system. The physiological and behavioural functions of these peptides have been clarified by both in vivo and in vitro studies. In spite of intensive investigations, the functions of endogenous BN-like peptides remain unclear. In order to specify these functions, our group and another laboratory generated by gene targeting mutant mice that lack one of the three BN-like peptide receptors found in mammals, ie neuromedin B receptor (NMB-R; BB1), gastrin-releasing peptide receptor (GRP-R; BB2), or bombesin receptor subtype-3 (BRS-3; BB3). Using these mutant mouse, we have found unexpected phenotypes, such as hyperphagia and obesity in the BRS-3-deficient mouse, and abnormal social behaviour in the GRP-R-deficient mouse. In the present study, we present our most recent findings in addition to previous studies and discuss the functions of BN-like peptides related to feeding and social behaviour from the point of view of knock-out mice studies.

Animals↗
PubMed2000

Influence of anteroposterior and mediolateral instability on range of motion after total knee arthroplasty: an ultrasonographic study.

Ultrasonographically, the femoral component and the tibial plate of total knee prostheses are strongly echogenic, while the high-density polyethylene insert is hypoechoic. This study evaluated the influence of mediolateral and anteroposterior stability after total knee arthroplasty (TKA) on range of motion using real-time monitoring with ultrasound. Mediolateral stress translation, which is increased by horizontal resection of more bone at the ends of the femur or tibia for easy prosthesis implantation, was examined on coronal scans at the level of the collateral ligaments. Anteroposterior drawer was examined on sagittal scans at the level of the patellar tendon. Mediolateral translation (0-10 mm; mean 2.24 mm) did not correlate with range of motion, while anteroposterior drawer (2-10 mm, mean 5.05 mm) correlated well with range of motion. These ultrasonographic findings suggest that horizontal over-resection of the ends of the femur and tibia contributed to joint laxity, which would not result in better ROM. Rollback and sliding of the femoral component on the tibia, which is believed to be correlated with anteroposterior drawer, may be important in achieving better range of motion and obtaining excellent results in TKA.

Hip Prosthesis↗
PubMed1999

Can intramedullary signal change on magnetic resonance imaging predict surgical outcome in cervical spondylotic myelopathy?

STUDY DESIGN: A retrospective study evaluating magnetic resonance imaging, computed tomographic myelography, and clinical parameters in patients with cervical spondylotic myelopathy. OBJECTIVES: To investigate whether magnetic resonance imaging can predict the surgical outcome in patients with cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: No previous studies have established whether areas of high signal intensity in T2-weighted magnetic resonance images can be a predictor of surgical outcomes. METHODS: Fifty patients with cervical spondylotic myelopathy were examined by magnetic resonance imaging and computed tomographic myelography before surgery and by delayed computed tomographic myelography after surgery. The correlation between the recovery rate and the clinical and imaging parameters was analyzed. RESULTS: The best prognostic factor was the transverse area of the spinal cord at maximum compression (correlation coefficient, R = 0.58). The presence of high signal intensity areas on T2-weighted magnetic resonance images correlated poorly with the recovery rate (R = -0.29). However, patients with multisegmental areas of high signal intensity on T2-weighted magnetic resonance images tended to have poor surgical results associated with muscle atrophy in the upper extremities. Postoperative delayed computed tomographic myelography showed that multisegmental areas of high signal intensity on T2-weighted magnetic resonance images probably represent cavitation in the central spinal cord. CONCLUSIONS: Patients with multisegmental areas of high signal intensity on T2-weighted magnetic resonance images tended to have poorer surgical results. However, the transverse area of the spinal cord at the level of maximum compression was a better prognostic indicator.

Aged↗
PubMed1999

Hyperresponsiveness to palatable and aversive taste stimuli in genetically obese (bombesin receptor subtype-3-deficient) mice.

Taste preference in obese mice was examined using genetically obese (bombesin receptor subtype-3: BRS-3 deficient) animals. Preference for either sodium saccharin (0.2%). sodium chloride (0.9%), citric acid (0.1%), or quinine sulfate (0.002%) solution was examined using a two-bottle test situation, and BRS-3 deficient mice not only showed a stronger preference for saccharin solution, but also a stronger aversive response to quinine solution, relative to wild-type littermates. Furthermore, a conditioned taste-aversion test measured the consumption of sodium saccharin (0.2%) and sodium chloride (0.9%) solutions after intraperitoneal injection of LiCl (0.3 M, 1 mg/kg), and BRS-3-deficient mice exhibited stronger aversion to both solutions than did control animals. In situ hybridization demonstrated that the BRS-3 gene is expressed in the parabrachial nucleus, the medial and central nuclei of the amygdala, and the hypothalamic nuclei such as paraventricular nucleus, all of which are known to be involved in taste perception. These results suggest that expression of the BRS-3 gene in these nuclei is important for the modulation of taste preference, as well as the development of obesity.

Analysis of Variance↗
PubMed1999

Effects of abdominal belts on intra-abdominal pressure, intra-muscular pressure in the erector spinae muscles and myoelectrical activities of trunk muscles.

OBJECTIVE: To evaluate the effects of abdominal belts on lifting performance, muscle activation, intra-abdominal pressure and intra-muscular pressure of the erector spinae muscles. DESIGN: Simultaneous measurement of intra-abdominal pressure, intra-muscular pressure of the erector spinae muscles was performed during the Valsalva maneuver and some isometric lift exertions. BACKGROUND: While several hypotheses have been suggested regarding the biomechanics of belts and performance has been found to increase when lifting with belts, very little is known about the modulating effects on trunk stiffness. At present, there is no reason to believe that spine tolerance to loads increases with belts. METHODS: An abdominal belt designed for weightlifting was used. Intra-abdominal pressure, intra-muscular pressure of the erector spinae muscles and myoelectric activities of trunk muscles (erector spinae, rectus abdominis and external oblique) were measured simultaneously during the Valsalva maneuver as well as three types of isometric lifting exertions (arm, leg and torso lift). A paired t-test was used to analyze for statistical differences between the two conditions (without-belt and with-belt) in intra-abdominal pressure, intra-muscular pressure of the erector spinae muscles and in the integrated EMG of the trunk muscles. RESULTS: Intra-muscular pressure of the erector spinae muscles increased significantly by wearing the abdominal belt during Valsalva maneuvers and during maximum isometric lifting exertions, while maximum isometric lifting capacity and peak intra-abdominal pressure were not affected. Integrated EMG of rectus abdominis increased significantly by wearing the abdominal belt during Valsalva maneuvers (after full inspiration) and during isometric leg lifting. CONCLUSIONS: Wearing abdominal belts raises intra-muscular pressure of the erector spinae muscles and appears to stiffen the trunk. Assuming that increased intra-muscular pressure of the erector spinae muscles stabilizes the lumbar spine, wearing abdominal belts may contribute to the stabilization during lifting exertions.

Abdominal Muscles↗
PubMed1999

Clinical significance of IgE-binding activity to enzymatic digests of ovomucoid in the diagnosis and the prediction of the outgrowing of egg white hypersensitivity.

BACKGROUND: We frequently encounter subjects without overt symptoms despite high IgE antibodies to egg white and its components. The measurements of these antibodies are not necessarily efficient for the diagnosis or the prediction of the outcome of egg allergy in children. METHODS: Specific IgE antibodies to egg white and its components, including ovomucoid, ovalbumin, ovotransferrin and lysozyme, were measured by direct RAST assays. IgE-binding activity to ovomucoid degraded by pepsin, trypsin and chymotrypsin was examined by RAST inhibition. Thirty subjects were divided into two groups with positive (n=18; mean age +/- SD = 42 +/-25 months) and negative (n=12; mean age +/- SD = 48 +/-31 months) oral challenge tests with egg white antigens. The individuals with positive results to the first challenge tests were given the second provocation tests at mean intervals of 32 months. IgE-binding activity of the sera collected on the first challenge to these ovomucoid fragments was compared between subjects with positive and negative reactions to the follow-up challenge tests. RESULTS: There were no significant differences in IgE antibody titers to egg white and its components between the positive and negative groups at the first and the second challenge tests. IgE-binding activity to ovomucoid digests after treatments with pepsin (p = 0.000008) and trypsin (p=0.037), except chymotrypsin (p=0.062), were significantly higher in subjects with positive challenge tests than in those with negative results. The difference was most remarkable in the IgE-binding to pepsin digests; the average concentrations (mean - SD and mean + SD) needed for 50% RAST inhibition in the positive group and in the negative group were 2.6 microg/ml (0.3 and 25) and 94.2 microg/ml (24.7 and 358.7), respectively. A significant difference was still observed in the inhibition tests using filtrates of pepsin digests with a membrane with MW 10,000 (p=0.014) and 3,000 (p=0.042) of cutoff. The concentration (mean= 0.8, mean - SD=0.2, mean + SD=3.4; microg/ml) of pepsin-treated ovomucoid required for 50% RAST inhibition in the subjects with positive second challenge results was significantly (p=0.033) lower than that (mean=6.8, mean-SD=0.6, mean + SD=73.9) of the negative group. CONCLUSION: IgE-binding activity to pepsin-digested ovomucoid was of diagnostic value to distinguish the challenge-positive subjects from the negative subjects. Subjects with high IgE-binding activity to pepsin-treated ovomucoid are unlikely to outgrow egg white allergy.

Adult↗
PubMed1998

Metabotropic glutamate receptor subtypes in axon terminals of projection fibers from the main and accessory olfactory bulbs: a light and electron microscopic immunohistochemical study in the rat.

Localization of metabotropic glutamate receptor subtypes, mGluR1, mGluR1alpha, mGluR2/3, mGluR4a, mGluR5, mGluR7a, mGluR7b, and mGluR8, was examined in some of the target areas of projection fibers from the main and accessory olfactory bulbs (MOB and AOB) by using subtype-specific antibodies. The superficial layer of the olfactory tubercle and layer Ia of the piriform cortex, the target areas of MOB, showed marked mGluR1-, mGluR5-, mGluR7a-, and mGluR8-like immunoreactivities (-LI), and rather weak mGluR2/3-LI. The periamygdaloid cortical region including the target areas of both MOB and AOB showed intense mGluR2/3-LI as well as marked mGluR1-, mGluR5-, mGluR7a-, and mGluR8-LI. No significant mGluR1alpha-, mGluR4a-, or mGluR7b-LI was seen in these regions. After transection of the lateral olfactory tract, mGluR2/3-, mGluR7a-, and mGluR8-LI were reduced markedly in the target regions on the side ipsilateral to the transection; no significant changes were detected in mGluR1- or mGluR5-LI. Double labeling experiments indicated light and electron microscopically colocalization of mGluR7a- and mGluR8-LI in axon terminals on dendritic shafts of presumed interneurons in the superficial layer of the olfactory tubercle and layer Ia of the piriform cortex. Electron microscopically mGluR2/3-LI was seen in preterminal and terminal portions of axons, whereas mGluR7a- and mGluR8-LI were associated with presynaptic membrane specialization. Immunolabeled axon terminals were filled with round synaptic vesicles and constituted asymmetric synapses with dendritic profiles. The results suggest that glutamate release from axon terminals of projection fibers from MOB and AOB is regulated presynaptically and differentially through mGluR2/3, mGluR7a, and/or mGluR8.

Animals↗
PubMed1998

Development of porous apatite ceramic for local delivery of chemotherapeutic agents.

An experimental study was conducted on a drug delivery system (DDS), using porous apatite ceramics (PAC): hydroxyapatite block (HAb) [Ca10(PO4)6(OH)2] having a porosity of 35-48% and pore size range of 50-300 microm, and beta-tricalcium phosphate block (TCP) [Ca3(PO4)2] having a porosity of 75-80% and pore size range of 100-400 microm, for sustained release of a chemotherapeutic agent. Methotrexate (MTX) was loaded in the pores of PAC blocks by centrifuging the blocks in MTX solution. Impregnation of MTX in PAC blocks (1 cm3) was confirmed by a magnetic resonance imaging (MRI) study using Gadolinium-DTPA enhancement. The MRI showed high signal intensity in the PAC, which was confirmed by dye loading into the pores. To estimate the MTX-releasing capability of the PAC, the blocks were stored in 3 mL of phosphate-buffered saline (PBS) at 37 degrees C and the PBS was replaced every 48 h. The amount of MTX released was assayed by high-performance liquid chromatography. This study showed that MTX-impregnated PAC (0.63-2.25 mg/block) released the drug in a steady manner and maintained its concentration (0.1-1.0 microg/mL) up to 12 days. This concentration is high enough to be effective against tumor cells. Chemotherapeutic agent-impregnated PAC, prepared by simple centrifugation, could be a valuable form of local chemotherapy when used as a strut graft to repair bone defects. This new DDS material could also be used as an adjuvant to extended curettage and provide a means to reduce the recurrence of tumors without risk of systemic toxicity.

Antimetabolites, Antineoplastic↗
PubMed1998

[Respiratory symptoms by oral challenge tests with egg white antigens in egg-allergic children].

One hundred and ninety one subjects showing histories of immediate hypersensitive response to egg white ingestion and/or positive IgE antibody titers specific for egg white were enrolled in double-blind placebo-controlled oral challenge with freeze and dried, heated or heated and ovomucoid-depleted egg white antigens. Seventy seven were male and 114 female, and their ages ranged from 11 month to 10 years 5 month; 118 of them had atopic dermatitis, seven had asthma and 33 had both atopic dermatitis and bronchial asthma and 33 had urticaria. One hundred four children developed 147 positive symptoms including 131 immediate reactions and 16 non-immediate reactions by oral challenge tests. Respiratory symptoms were observed in 25 cases (17%) including cough alone in 12 cases (8.2%), and both wheezing and cough in 13 cases (8.8%). These were all observed as immediate reactions and accompanied with dermal symptoms. Frequency of respiratory symptoms correlated with specific IgE antibody titers for egg white. Heated and ovomucoid-depleted egg white was more hypoallergenic that heated or freeze and dried egg white with respect to respiratory symptoms as well as other symptoms. We concluded that respiratory symptoms were provoked through oral challenges with egg white in a part of egg-allergic children.

Administration, Oral↗
PubMed1997

Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity.

Mammalian bombesin-like peptides are widely distributed in the central nervous system as well as in the gastrointestinal tract, where they modulate smooth-muscle contraction, exocrine and endocrine processes, metabolism and behaviour. They bind to G-protein-coupled receptors on the cell surface to elicit their effects. Bombesin-like peptide receptors cloned so far include, gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor (NMB-R), and bombesin receptor subtype-3 (BRS-3). However, despite the molecular characterization of BRS-3, determination of its function has been difficult as a result of its low affinity for bombesin and its lack of an identified natural ligand. We have generated BRS-3-deficient mice in an attempt to determine the in vivo function of the receptor. Mice lacking functional BRS-3 developed a mild obesity, associated with hypertension and impairment of glucose metabolism. They also exhibited reduced metabolic rate, increased feeding efficiency and subsequent hyperphagia. Our data suggest that BRS-3 is required for the regulation of endocrine processes and metabolism responsible for energy balance and adiposity. BRS-3-deficient mice provide a useful new model for the investigation of human obesity and associated diseases.

Adipose Tissue, Brown↗
PubMed1997

Generation and characterization of mice lacking gastrin-releasing peptide receptor.

Gastrin-releasing peptide (GRP) is a mammalian bombesin-like peptide which is widely distributed in the central nervous system as well as in the gastrointestinal tract. GRP binds to its high affinity receptor (GRPR) to elicit a wide spectrum of biological effects on behavior, digestion, and metabolism. To define the in vivo function of GRPR, we generated GRPR null mutant mice by gene targeting. The intracerebroventricular administration of GRP caused hypothermia in wild-type mice, but not in mutant mice. The GRPR deficient mice showed significantly increased locomotor activity during the dark period, and social responses scored by sniffing, mounting, and approaching behaviors against an intruder. Aggressive scores such as fighting and biting were not altered in the mutant mice. These phenotypes were observed in mice generated from two independent ES cell clones and backcrossed to a C57BL/6J background. The GRPR deficient mice should be useful for studying the bombesin system in vivo.

Animals↗
PubMed1997

Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus.

Neurotransmission in the hippocampus is modulated variously through presynaptic metabotropic glutamate receptors (mGluRs). To establish the precise localization of presynaptic mGluRs in the rat hippocampus, we used subtype-specific antibodies for eight mGluRs (mGluR1-mGluR8) for immunohistochemistry combined with lesioning of the three major hippocampal pathways: the perforant path, mossy fiber, and Schaffer collateral. Immunoreactivity for group II (mGluR2) and group III (mGluR4a, mGluR7a, mGluR7b, and mGluR8) mGluRs was predominantly localized to presynaptic elements, whereas that for group I mGluRs (mGluR1 and mGluR5) was localized to postsynaptic elements. The medial perforant path was strongly immunoreactive for mGluR2 and mGluR7a throughout the hippocampus, and the lateral perforant path was prominently immunoreactive for mGluR8 in the dentate gyrus and CA3 area. The mossy fiber was labeled for mGluR2, mGluR7a, and mGluR7b, whereas the Schaffer collateral was labeled only for mGluR7a. Electron microscopy further revealed the spatial segregation of group II and group III mGluRs within presynaptic elements. Immunolabeling for the group III receptors was predominantly observed in presynaptic active zones of asymmetrical and symmetrical synapses, whereas that for the group II receptor (mGluR2) was found in preterminal rather than terminal portions of axons. Target cell-specific segregation of receptors, first reported for mGluR7a (Shigemoto et al,., 1996), was also apparent for the other group III mGluRs, suggesting that transmitter release is differentially regulated by 2-amino-4-phosphonobutyrate-sensitive mGluRs in individual synapses on single axons according to the identity of postsynaptic neurons.

Animals↗
PubMed1997

Cloning and expression of the neuromedin B receptor and the third subtype of bombesin receptor genes in the mouse.

We cloned the genes for the mouse homologue of the neuromedin B receptor (NMB-R) and the bombesin receptor subtype 3 (BRS-3). Both receptor genes consist of three exons with well-conserved intron-exon borders. Although the NMB-R gene spans more than 10 kb, the BRS-3 gene spans only about 4 kb. Comparison of the mouse and human receptor sequences indicates 90% (NMB-R) and 85% (BRS-3) sequence homology at the amino-acid level. In the adult mouse, the NMB-R mRNA is expressed in the brain, testis, esophagus, intestine and uterus, whereas the BRS-3 mRNA is expressed predominantly in the brain. In the brain, the NMB-R gene expression is prominent in the thalamic and olfactory regions, and the BRS-3 gene is expressed particularly in the hypothalamic region. In mouse testis, the NMB-R gene expression is prominent, and the expression of BRS-3 mRNA is barely detected. In contrast, BRS-3 has been shown to be expressed in rat testis and guinea-pig uterus, therefore it is possible that a different subtype of the bombesin receptor mediates the same response in different species. Together with the mouse GRP-R gene cloned previously, cloning of the mouse NMB-R and BRS-3 genes permits comparison of function and structure of the three bombesin receptor subtypes in the mouse.

Animals↗
PubMed1997

Density dependent change of myristoylated proteins in C3H10T1/2 fibroblasts and their transformants.

We have examined the pattern of protein myristoylation in C3H10T1/2 fibroblasts during cell growth. During the growing phase of 10T1/2 cells, several proteins were radiolabelled with [3H]myristate, and among them proteins with molecular masses of 22, 35, a doublet of 42-45 and 67 kDa were labelled predominantly. The extent of myristoylation in each of these proteins changed with cell density. The amount of radioactivity incorporated into the 22 kDa protein in 10T1/2 cells decreased with increasing cell density and remained at a low level during the stationary phase. In contrast, the incorporation into the 67 kDa protein increased parallel to cell density. The density-dependent change of myristoylation was not observed in any of the transformants of 10T1/2 cells thus far examined. The 67 kDa protein was identified as MARCKS (myristoylated alanine-rich C kinase substrate) by immunoprecipitation with an anti-MARCKS antibody. By Western blot analysis, we found that the amount of MARCKS in 10T1/2 cells increased significantly analogous with cell density. Therefore, it is possible that MARCKS and the 22 kDa protein play a role in contact-mediated cell signalling in 10T1/2 cells, but the mechanism is lost in transformed cells.

Animals↗
PubMed1997

Allergenic activity of heated and ovomucoid-depleted egg white.

BACKGROUND: No egg white products have been clearly proven to be hypoallergenic. The role of egg white proteins in allergic reactions to eggs is still debatable. OBJECTIVE: This study was designed to determine the importance of ovomucoid, an egg white protein, in the development of allergies to egg white. METHODS: We performed a double-blind, placebo-controlled food challenge in subjects with high levels of IgE antibodies for egg white to compare the allergenicities of heated and ovomucoid-depleted egg white, freeze-dried egg white, and heated egg white. Levels of IgE antibodies for egg white, ovomucoid, ovalbumin, ovotransferrin, and lysozyme were measured in serum by RAST. RESULTS: Twenty-one of 38 subjects with positive challenge responses to freeze-dried egg white had negative challenge responses to heated egg white, whereas 16 of 17 subjects (94.1%) with positive responses to heated egg white did not respond to the heated and ovomucoid-depleted egg white challenge. The subjects with positive challenge responses to freeze-dried egg white tended to have higher IgE antibody values to ovomucoid than those with negative responses. IgE antibody levels to ovomucoid were significantly higher in subjects with positive responses to a challenge with heated egg white than in those with no response. There were no significant differences in the levels of IgE antibodies to the other proteins, except ovomucoid, in the negative-response and positive-response groups in challenge tests with freeze-dried and heated egg white. CONCLUSION: The heated and ovomucoid-depleted egg white preparation was less allergenic than heated or freeze-dried preparations. Ovomucoid has a more important role in the pathogenesis of allergic reactions to egg white than other proteins in egg white.

Allergens↗
PubMed1997

Antibiotic-loaded hydroxyapatite blocks in the treatment of experimental osteomyelitis in rats.

A novel drug delivery system for osteomyelitis was developed in which a porous hydroxyapatite block (HAB) is loaded with antibiotic by a centrifugation method. In this study, implantation of HABs loaded with the aminoglycoside antibiotic, arbekacin, were tested in established Staphylococcus aureus osteomyelitis in the proximal tibia of rats after debridement of the marrow cavity. The animals were observed for radiographic signs of infection and tissue was examined histologically. The infections were also evaluated by bone cultures. Bacterial counts were statistically lower in rats implanted with an antibiotic-loaded HAB than in those given a drug-free HAB. Radiographical and histological observations also showed beneficial effects of the antibiotic-loaded implant. The results suggest that the centrifugation method for loading HABs provides a simple drug delivery system. These antibiotic-loaded HABs may be useful for filling grafts in osteomyelitis.

Aminoglycosides↗
PubMed1997

[Assessment of allergenic activity of heated and ovomucoid-depleted egg white].

We investigated allergenic activity of heated and ovomucoid (OM)-depleted egg white by RAST inhibition tests, skin tests and and oral challenge tests. Freeze-dried egg white, OM and ovalbumin (OA) were coupled with CNBr-activated paper discs. Freeze-dried, heated, and heated and OM-depleted egg white antigens were used as inhibitors in RAST inhibition tests. Freeze-dried egg white significantly inhibited the IgE-binding to freeze-dried egg-white-, OM- and OA-discs. Heated egg white showed a significant inhibition against only OM-disc, but heated and OM-depleted egg white didn't effectively suppress IgE-binding to all discs. Fifty-six patients were subjected for skin tests and 27 patients for oral challenge tests with freeze-dried egg white, heated egg white and heated and OM-depleted egg white. Eighteen of 25 subjects with positive prick tests results to freeze-dried egg white showed negative results to heated egg white. Four of 7 cases with positive prick test results to heated egg white gave negative results to heated and OM-depleted egg white. 20-minutes patch tests showed almost similar results to prick tests. Four of 8 subjects showing positive oral challenge tests with freeze-dried egg white were negative to heated egg white. All of 4 with positive oral challenge tests by heated egg white were negative results to heated and OM-depleted egg white. These evidence indicated that heated and OM-depleted egg white was more hypoallergenic than heated egg white.

Allergens↗