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Biomedical subjects

K Hayakawa

Publications and source records attributed to K Hayakawa.

At least 127 records · Page 7Linked to original sources
PubMed1999

Apoptosis and appearance of Trp53-positive micronuclei in murine tumors with different radioresponses in vivo.

The purpose of this paper is to determine the relationship between the response to radiation and the appearance of apoptosis and micronuclei with Trp53 protein in murine tumors after irradiation. Two murine tumors, EL4, which was derived from a mouse lymphoma, and FM3A, which was derived from a mouse mammary carcinoma, were locally irradiated with 15 Gy and sections were stained with H&E and an anti-Trp53 antibody. The response to radiation was greater in EL4 tumors than in FM3A tumors. The frequency of apoptotic cells in EL4 tumors was 6.1 +/- 1.2% at time zero, reached a peak of 36.3 +/- 3. 8% at 6 h, and then decreased with time through 72 h to 2.5 +/- 1.5% after 15 Gy irradiation. In FM3A tumors, no apoptotic cells were detected at 0, 1, 3, 6 or 24 h after exposure. At 48 and 72 h, the frequency was only 3.0 +/- 0.6% and 1.3 +/- 0.3%. Apoptotic cells increased significantly at 3, 6 and 24 h after irradiation in EL4 tumors (P < 0.008) and at 48 and 72 h in FM3A tumors (P < 0.006). The frequency of Trp53-positive cells was 17.9 +/- 2.2 and 15.2 +/- 2.3% at time zero in EL4 and FM3A tumors, respectively, increased to 74.5 +/- 4.5% in EL4 cells (P = 0.001), and increased to 33.9 +/- 1. 1% in FM3A cells (P = 0.005) 1 h after irradiation. Trp53-positive micronuclei appeared in cells in both tumors from 24 to 72 h after irradiation. The frequency of Trp53-positive micronuclei was 3.8 +/- 0.5 and 13.5 +/- 1.3% at 24 h in EL4 and FM3A tumors, respectively, and gradually decreased by 72 h. After exposure to 15 Gy, Trp53-positive micronuclei increased significantly in FM3A tumors compared to EL4 tumors at both 24 and 48 h (P < 0.02). The frequency of these micronuclei increased with increasing dose in FM3A tumors, and the difference between these percentages after 3 Gy and after 5, 10 and 15 Gy was significant (P < 0.02). Many apoptotic cells were observed in the radiosensitive EL4 tumor after irradiation. Death by apoptosis may be related to an early response to radiation in these tumors. The appearance of micronuclei may be an important mechanism of cell death in FM3A tumors in which no apoptosis was induced.

Animals↗
PubMed1999

Giant cell tumor of the thoracic spine simulating mediastinal neoplasm.

A case of giant cell tumor of the thoracic spine simulating mediastinal neoplasm was identified on plain films, CT scans, MR images, and with scintigraphy. CT showed a hypervascular soft-tissue mass with shell-like calcification in the right upper mediastinum. MR imaging showed a collapse of the T1 vertebral body and a mass extending to the mediastinum. The mass had a low signal on T1-weighted MR images and a predominantly high signal on T2-weighted images with heterogeneity. Technetium-99m methylene diphosphonate bone scintigraphy showed intense uptake in both the T1 and marginal parts of the mediastinal mass. There was no accumulation of gallium-67 citrate, but 18-fluorine fluorodeoxyglucose positron emission tomography showed marked uptake. The variation in these imaging findings played an important role in the differential diagnosis of this uncommon mediastinal mass.

Adult↗
PubMed1998

Selective ability of mouse CD1 to present glycolipids: alpha-galactosylceramide specifically stimulates V alpha 14+ NK T lymphocytes.

Mouse CD1 (mCD1) glycoproteins are known to present peptides, while human CD1 molecules present glycolipids. In mice, mCD1-autoreactive NK T cells play critical roles in various immune responses, through the secretion of high amounts of cytokines. This study was initiated to determine whether glycolipids are involved in the autorecognition of mCD1 by NK T cells. Alpha-galactosylceramide (alpha-GalCer) was the only glycolipid tested capable of eliciting an mCD1-restricted response by splenic T cells. Moreover, splenic T cells derived from mCD1-deficient mice were not stimulated by alpha-GalCer, suggesting that the responsive T cells are selected by mCD1. Using cytoflow techniques, we confirmed that, in response to alpha-GalCer, IFN-gamma-secreting cells displayed an NK T cell phenotype. The predominance of IFN-gamma vs IL-4, however, is determined by the type of mCD1+ APC, suggesting the potential for APC regulation of cytokine production by NK T cells. Among a panel of 10 mCD1-autoreactive T cell hybridomas, only the ones that express the typical V alpha 14 J alpha 281 TCR rearrangement of NK T cells responded to alpha-GalCer. Fixation or treatment of mCD1+ APCs with an inhibitor of endosomal acidification and the use of mCD1 mutants unable to traffic through endosome still allowed alpha-GalCer to stimulate NK T cells. Thus, endosomal trafficking and Ag processing are not required for glycolipid recognition. In summary, alpha-GalCer might be the autologous ligand, or a mimic of a glycolipid ligand, involved in the mCD1-mediated stimulation of NK T cells.

Animals↗
PubMed1998

Discovery of IRL 3461: a novel and potent endothelin antagonist with balanced ETA/ETB affinity.

IRL 3461, N-butanesulfonyl-[N-(3,5-dimethylbenzoyl)-N-methyl-3-[4-(5-+ ++isoxazolyl) -phenyl]-alanyl]-(L)-valineamide, a potent and bifunctional (ETA + ETB) [Ki(ETA) = 1.8 nM, Ki(ETB) = 1.2 nM] antagonist was discovered by structural modification of IRL 2500, an ETB selective antagonist. IRL 3461 was found to be stable on incubation with human, rat, mouse, and guinea pig plasmas.

Animals↗
PubMed1998

Stereoselective synthesis of a novel and bifunctional endothelin antagonist, IRL 3630.

IRL 3630 (3), a single enantiomer of IRL 3461 with more potency was identified. Coupling reaction of the racemic fragment (1) with the chiral (L)-valinesulfonamide (2) under a biphasic solvent system (CH2Cl2-H2O) successfully led to the predominant formation of the desired isomer (3) with concomitant isomerization of 1. IRL 3630, N-butanesulfonyl-[N-(3,5-dimethylbenzoyl)-N-methyl-3-[4-(5-+ ++isoxazolyl) -phenyl]-(D)-alanyl]-(L)-valineamide, is a highly potent and bifunctional (ETA + ETB) antagonist [Ki(ETA) = 1.5 nM, Ki(ETB) = 1.2 nM].

Animals↗
PubMed1998

Beta-adrenoceptor subtypes in the ureteral smooth muscle of rats, rabbits and dogs.

We investigated the beta-adrenoceptor subtypes mediating ureteral relaxation in rats, rabbits and dogs. The relaxing effects of beta-adrenoceptor agonists were evaluated on KCl-induced ureteral contractions. The rank order of potency of the catecholamines tested was isoprenaline > noradrenaline > adrenaline in rat ureter; isoprenaline > adrenaline > noradrenaline in rabbit ureter; only isoprenaline was effective in canine tissues. The beta1-adrenoceptor agonist, dobutamine, produced relaxation of rat ureter. The beta2-adrenoceptor agonist, procaterol, produced more significant relaxation of rabbit ureter than did dobutamine. CL-316243 [(R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethylamino]propyl]-1,3-b enzodioxole-2,2-dicarboxylate] and CGP-12177A [(+/-)[4-[3[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-+ ++benzimidazol-2-one hydrochloride], beta3-adrenoceptor agonists, were more effective in relaxing canine ureter than were dobutamine and procaterol. Isoprenaline-induced relaxation was antagonized by a beta1-adrenoceptor antagonist, CGP-20712A [2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4-trifluoromethyl)1H-imidazol e-2-yl)phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulphonate], in rats and by a beta2-adrenoceptor antagonist, ICI-118,551 [(+/-)-1-[(2,3-dihydro-7-methyl- 1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride], in rabbits. The non-selective beta-adrenoceptor antagonist, bupranolol, antagonized isoprenaline-induced relaxation in all species tested. In conclusion, beta-adrenoceptor agonists may relax ureter by stimulating mainly beta1-adrenoceptors in rats, beta2-adrenoceptors in rabbits and mainly beta3-adrenoceptors in dogs.

Adrenergic beta-Agonists↗
PubMed1998

NGF prevention of neurotoxicity induced by cisplatin, vincristine and taxol depends on toxicity of each drug and NGF treatment schedule: in vitro study of adult rat sympathetic ganglion explants.

The simultaneous administration of nerve growth factor (NGF) has been found to prevent experimental neuropathies induced by anti-cancer drugs such as cisplatin, vincristine and taxol. However, it is clinically important to know whether NGF is beneficial once the neuropathy is already manifest. We established a bioassay system to examine the preventive effects of NGF in various treatment schedules. NGF significantly prevented the inhibition of neurite outgrowth by vincristine and taxol regardless of treatment schedules. The pre-treatment and co-treatment schedules were effective against cisplatin, but the post-treatment schedule was not. With regard to the neurite and nerve cell population densities, only the cisplatin group treated with NGF showed lower values than the control. These results indicate that NGF-treatment is effective for the toxic sympathetic nerve injury induced by vincristine and taxol regardless of the treatment schedule, but is not protective against cisplatin-induced nerve cell injury.

Analysis of Variance↗
PubMed1998

X-ray absorption of bromonaphthalene dissolved in supercritical fluid xenon.

The results of Br K-edge X-ray absorption measurements of 1-bromonaphthalene dissolved in supercritical fluid Xe are reported. As the pressure of Xe confined in a high-pressure cell is increased, the absorption spectrum of bromonaphthalene gradually appears, showing that Xe in the supercritical fluid state solvates the bromonaphthalene molecule. The spectrum of the dissolved sample shows a remarkable difference from that of the pure liquid sample in the near-edge region of the X-ray absorption spectrum, reflecting the interaction of the solute material with solvent Xe. Ab initio full multiple-scattering calculations can reproduce the spectral features qualitatively. A large value of the Debye-Waller factor must be introduced to give the best fit, corresponding to a large degree of spatial disorder and violent thermal vibration of the Xe atoms around the Br atom.

Journal Article↗
PubMed1998

Radiotherapeutic Management of Brain Metastases from Breast Cancer.

We have reviewed the medical records of 28 breast cancer patients with brainmetastases who were treated with radiotherapy at our clinic from 1980 through 1994(4 patients, postoperatively; 24 patients, radiotherapy alone). Radiotherapy was delivered as whole brain irradiation using lateral opposed 10 MV X-rays. Tenpatients received an additional boost to a reduced field. One patient was treated with localized stereotactic irradiation alone. The radiation dose for tumorsranged from 32 Gy to 60 Gy(mean, 49 Gy)in 2 or 3 Gy daily fractionated doses. The brain was the first site of metastatic involvement in only two patients. In the 26 evaluable patients, neurologic functional improvement was achieved in 24 patients(92%)with complete response(CR)in 12 patients(46%)and partial response(PR)in 12 patients(46%). The survival rates from the initial treatment were 39% at 5 years and 16% at 10 years(median survival time, 50 months), and those after treatment of brain metastases were 29% at one year and 18% at 2 years(median survival time, 6 months). Performance status tended to be associated with survival(p=0.10), and the presence of liver metastasis was the most important risk factor concerning survival(p=0.056). Two patients suffered severe chronic complications.One patient developed severe dementia after whole brain irradiation with a total dose of 45 Gy in 3 Gy daily fractionated dose, and another patient developed widespread brain necrosis after combined radiotherapy with intrathecal local infusion of methotrexate. Radiotherapeutic management is useful for breast cancer patients with brain metastasis, and long-term survival may also be possible even if patients have preexisting extracranial metastases, except for hepatic involvement. Radiation-related complications should therefore be avoided in these patients.

Journal Article↗
PubMed1998

Unique molecular surface features of in vivo tolerized T cells.

Differential expression of surface markers can frequently be used to distinguish functional subsets of T cells, yet a surface phenotype unique to T cells induced into an anergic state has not been described. Here, we report that CD4 T cells rendered anergic in vivo by superantigen can be identified by loss of the 6C10 T cell marker. Inoculation of Vbeta8.1 T cell antigen receptor (TCR) transgenic mice with a Vbeta8.1-reactive minor lymphocyte-stimulating superantigen (Mls-1(a)) induces tolerance to Mls-1(a) by clonal anergy. CD4 lymph node T cells from Mls-1(a) inoculated transgenic mice enriched for the 6C10(-) phenotype neither proliferate nor produce interleukin-2 upon TCR engagement, whereas 6C10(+) CD4 T cells retain responsiveness. Analysis of T cell memory markers demonstrate that 6C10(-) T cells remain 3G11(hi) but express heterogeneous levels of CD45RB, CD62L, CD44, and the CD69 early activation marker, suggesting that T cells at various degrees of activation can be functionally anergic. These studies demonstrate that anergic T cells can be purified based on 6C10 expression permitting examination of issues concerning biochemical and biological features specific to T cell anergy.

Animals↗
PubMed1998

A novel mechanism for B cell repertoire maturation based on response by B cell precursors to pre-B receptor assembly.

The expression of different sets of immunoglobulin specificities by fetal and adult B lymphocytes is a long-standing puzzle in immunology. Recently it has become clear that production of immunoglobulin mu heavy chain and subsequent assembly with a surrogate light chain to form the pre-B cell receptor complex is critical for development of B cells. Here we show that instead of promoting pre-B cell progression as in adult bone marrow, this complex inhibits pre-B cell growth in fetal liver. Curiously, we identify a fetal-associated VH11 mu heavy chain that allows continued pre-B proliferation in fetal liver. Interestingly, this heavy chain does not associate efficiently with a surrogate light chain, providing a previously unrecognized mechanism for skewing the expression of distinctive VH genes toward fetal through early neonatal life.

Animals↗
PubMed1998

Microorganism inactivation using high-pressure generation in sealed vessels under sub-zero temperature.

In order to test the possibility of utilizing high pressure in bioscience and biotechnology, a simple method for high-pressure generation and its use for microbial inactivation have been studied. When a pressure vessel was filled with water, sealed tightly and cooled to sub-zero temperatures, high pressure was generated in the vessel. The pressure generation was 60 MPa at -5 degrees C, 103 MPa at -10 degrees C, and 140 MPa at -15 degrees C, -20 degrees C, and -22 degrees C. The high pressure generated inactivated microorganisms effectively: yeasts (Saccharomyces cerevisiae and Zygosaccharomyces rouxii), bacteria (Lactobacillus brevis and Eschericia coli), and fungi (Aspergillus niger and Aspergillus oryzae) were completely inactivated when stored in sealed vessels -20 degrees C for 24 h. However, Staphylococcus aureus was only partly inactivated under the same conditions. This method opens up a new application of high pressure for storing, transporting, and sterilizing of foods and biological materials.

Bacteria↗
PubMed1998

Subcellular localization of dystrophin and vinculin in cardiac muscle fibers and fibers of the conduction system of the chicken ventricle.

The subcellular localization of dystrophin and vinculin was investigated in cardiac muscle fibers and fibers of the conduction system of the chicken ventricle by immunofluorescence confocal microscopy. In ventricular cardiac muscle fibers, strong staining with antibody against dystrophin appeared as regularly arranged transverse striations at the sarcolemmal surface, and faint but uniform staining was seen in narrow strips between these striations. In fibers of the ventricular conduction system, the sarcolemma was stained uniformly with this antibody, but strong staining was found as regular striations in many areas and as scattered patches in other areas of the sarcolemma. These intensely stained striations and scattered patches of dystrophin were colocalized with those of vinculin. Because dystrophin striations were located at the level of Z bands of the underlying myofibrils, they were regarded as the concentration of this protein at costameres together with vinculin. In fibers of the conduction system, myofibrils were close to the sarcolemma where dystrophin and vinculin assumed a striated pattern, at some distance from the cell membrane where these proteins exhibited a patchy distribution, and distant from the sarcolemma where dystrophin was uniformly distributed. These data suggest that the distribution patterns of dystrophin reflect the degree of association between the sarcolemma and underlying myofibrils.

Amino Acid Sequence↗
PubMed1998

Gastrojejunal fistula caused by gastric ulcer.

We report a case of gastrojejunal fistula caused by benign gastric ulcer, a very rare condition. The patient was an 81-year-old-woman who had had multiple recurrences of gastric ulcer. She also had diabetes mellitus. She was admitted to our hospital because of a left femoral head fracture, necessitating a mechanical bone head exchange operation. She had severe abdominal pain and anemia on the 48th postoperative day. Gastroendoscopic examination revealed a giant ulcer with a long-axis diameter of more than 5cm on the lesser curvature of the gastric body. She was treated with intravenous famotidine and all oral intake was restricted; her symptoms were alleviated. Two weeks later, a fistula had formed between the stomach and the jejunum just anal to the duodeno-jejunal flexure. She was placed on an ulcer diet, and was discharged with no symptoms on the 151st postoperative day. She has remained asymptomatic for 1 1/2, years to date. Lack of H2-antagonist administration, operative stress, and administration of ipriflavone appeared to have induced gastric ulcer recurrence, and formation of the fistula between the stomach and the jejunum seemed to have been facilitated by the patient being very lean and having minimal mesenteric adipose tissue.

Aged↗
PubMed1998

Malignant neuroendocrine tumor presenting a huge mediastinal mass controlled with radiation therapy.

A case of malignant neuroendocrine tumor presenting a huge mediastinal mass controlled with radiation therapy is reported. A thoracotomy was performed on a 57-year-old male and a mass was found to invade the trachea, main bronchus, and left atrium. The tumor was unresectable. Subsequently, cisplatin was administered, but the tumor grew in size and radiation therapy was recommended. The tumor responded well to thoracic irradiation (56 Gy) and disappeared. Three months later, lymph nodes metastases were noted in the retrocrural and upper abdominal paraaortic regions, but these were controlled again with palliative irradiation. Without further treatment, he survived free of disease for over 5 years. Specimens obtained during the thoracotomy showed that the tumor consisted mainly of small round cells with a rosette formation. Immunohistochemically the tumor was positive to NSE and slightly positive to keratin, but negative to LCA, L26, UCLH-1, EMA, Leu7, and chromogranin, suggesting a malignant tumor derived from neuroendocrine tissue.

Diagnosis, Differential↗
PubMed1998

Cranioplasty with split lateral skull plate segments for reconstruction of skull defects.

This paper reports the use of cranioplasty using segments of split lateral skull plate to correct large skull defects (larger than 8 x 8 cm). The subjects consisted of 10 patients with head trauma who had undergone decompression surgery, and two patients who had undergone tumour resection. Bone grafts were obtained by cutting approximately 2 cm wide strips from the lateral skull plate using a bone saw that was inserted from a free margin of the bone defects. By cutting strips laterally from the bone defect, the necessary amount of split lateral skull plate can be obtained without performing craniotomy. The pieces of split lateral skull plate are then fixed to the defect using wire or titanium mini-plates. At this point, the selection of bone grafts that match the curvature of the dura mater is important, so that no dead spaces are created between the dura mater and the bone grafts. Infection was not detected in any of the 12 patients, and all bone grafts took completely. One of the 12 patients suffered from a pathological fracture and bone resorption 6 months after surgery. The fracture occurred because the use of basket-shaped reconstruction plates resulted in large spaces between the plate segments, and in addition the intracranial pressure was kept low by a V-P shunt, thus rendering the patient more vulnerable to atmospheric pressure.

Adolescent↗