Biomedical subjects

K Hayakawa

Publications and source records attributed to K Hayakawa.

At least 55 records · Page 3Linked to original sources

PubMed2001

Induction of cytochrome P450 1B1 in lung, liver and kidney of rats exposed to diesel exhaust.

We have shown previously that diesel exhaust particle (DEP) extracts (DEPE) and 1-nitropyrene were genotoxically activated by human cytochrome P450 1B1 in SOS/umu assay. In this study, the in vivo induction of P450 family 1 enzymes in rats by exposure to diesel exhaust was investigated with regard to mRNA levels, P450 enzyme content, drug oxidation activities in the microsomes and umu gene expression of typical P450 substrates and DEPE itself catalyzed by the microsomes. Male Fischer 344 rats (4 weeks old) were exposed to 0.3 and 3.0 mg/m(3) DEP for 12 h per day for 4 weeks; the former dose corresponded to the typical daily airborne particle concentration. The levels of mRNA of rat P450 1B1 and P450 1A1 in the lung and liver were significantly increased 1.1-1.4-fold by exposure to 0.3 mg/m(3) DEP. Diesel exhaust particle extracts induced umu gene expression in Salmonella typhimurium TA1535/pSK1002 in the absence of a functional P450 system and were further activated by human recombinant P450 1B1. Using an O-acetyltransferase overexpressing Salmonella strain, genotoxic activation of P450 1B1 marker chemicals (1-nitropyrene, 1-aminopyrene and DEPE) by lung, liver and kidney microsomes was increased 1.7-4.2-, 1.4-1.5- and 1.0-1.3-fold, respectively, by exposure to 0.3 mg/m(3) DEP. Activation of 3-amino-1,4-dimethyl-5H-pyrido [4,3-b]indole (Trp-P-1; marker for P450 1A1) by lung microsomes and the P450 1A2 content in liver microsomes were slightly increased by exposure to 3.0 mg/m(3) DEP. This is the first report to suggest that typical daily contaminant levels (0.3 mg particle/m(3)) of diesel exhaust can induce P450 1B1 in rats and that the induced P450 1B1 may catalyze the genotoxic activation of DEP.

Animals↗

PubMed2001

Small cell lung cancer with a brain metastasis controlled for 5 years: a case report.

We report a case of small cell lung cancer whose initial presentation was a solitary brain metastasis. On chest radiography the primary tumor was unclear and only detected by bronchofiberscopy. A small single pulmonary metastasis was noted in the right lower lobe. Subtotal resection and external irradiation were applied to the brain tumor and external irradiation was applied to the lung. Concurrently one course of systemic chemotherapy was administered. The tumors in the brain and lung had disappeared by the end of the treatment. The patient has been alive and well for 5 years without recurrence.

Brain Neoplasms↗

PubMed2001

Toxicity and health-related quality of life during and after high dose rate brachytherapy followed by external beam radiotherapy for prostate cancer.

BACKGROUND: The optimal protocol for combining high dose rate brachytherapy and external beam irradiation as treatment for localized prostate cancer is unknown. Toxicity rates and clinical and biochemical outcomes should be evaluated to validate the current treatment protocol. METHODS: Fifty-eight patients were treated for prostate cancer with high dose rate brachytherapy followed by 30 Gy of external beam radiation therapy. Toxicity during treatment and for 12-18 months thereafter, and treatment-related morbidity, were evaluated. Physician-assessed treatment-related toxicity was graded at the time of occurrence using the Radiation Therapy Oncology Group morbidity criteria. Four separate self-administered questionnaires were used to collect longitudinally demographic data and general and prostate disease-related measures of quality of life. RESULTS: Various degrees of rectal bleeding due to radiation proctitis were experienced by 13 patients (22%) at a median time of 11 months. Two of these patients needed hospitalization to undergo laser coagulation of the rectal mucosa. Study patients had statistically significant decreases in five SF-36 domains during the first month of treatment. All measures recovered by 12 months. Sexual function was not affected by irradiation. Lower urinary tract symptoms assessed by IPSS/QOL scores worsened significantly during the first month of treatment but later recovered to baseline levels. Physician-assessed RTOG scores failed to detect these changes. CONCLUSIONS: Morbidity associated with combined radiation therapy was greatest during the first month of treatment and affected quality of life significantly. Most measures recovered to baseline levels by 12 months following radiation therapy. Although the current protocol appears acceptable, measures should be taken to decrease treatment-related morbidity further.

Adult↗

PubMed2001

Biological cell survival mapping for radiofrequency intracavitary hyperthermia combined with simultaneous high dose-rate intracavitary irradiation.

We examined the best way to combine recently developed radiofrequency intracavitary hyperthermia with simultaneous high dose-rate intracavitary brachytherapy in an original experimental model. Temperature distribution was measured with an experimental phantom which was immersed in a water bath with the temperature controlled at 37 degrees C. Radiation dose distribution was calculated with a treatment-planning computer. Cell survival was measured by colony assay with HeLa-TG cells in vitro. Radiation dose response at 1 - 7 Gy and time response with hyperthermia in the range of 40 - 46 degrees C were estimated. Radiation dose-response curves in simultaneous treatment with hyperthermia for 30 min at 37 to 46 degrees C were estimated and the surviving fractions in combined treatment were plotted against temperature. For intracavitary radiation alone, cell survival rates increased with increasing distance from the source. For intracavitary hyperthermia alone, the maximum temperature was observed at a depth of 13 mm from the surface of the applicator under suitable treatment conditions. Homogeneous cell killing from the surface of the applicator to a tumor depth of 13 mm was observed under a specific treatment condition. Our experimental model is useful for evaluating the best simultaneous combined treatment.

Brachytherapy↗

PubMed2001

B cell development pathways.

B cell development is a highly regulated process whereby functional peripheral subsets are produced from hematopoietic stem cells, in the fetal liver before birth and in the bone marrow afterward. Here we review progress in understanding some aspects of this process in the mouse bone marrow, focusing on delineation of the earliest stages of commitment, on pre-B cell receptor selection, and B cell tolerance during the immature-to-mature B cell transition. Then we note some of the distinctions in hematopoiesis and pre-B selection between fetal liver and adult bone marrow, drawing a connection from fetal development to B-1/CD5(+) B cells. Finally, focusing on CD5(+) cells, we consider the forces that influence the generation and maintenance of this distinctive peripheral B cell population, enriched for natural autoreactive specificities that are encoded by particular germline V(H)-V(L) combinations.

Animals↗

PubMed2001

Mechanism of burn injury during magnetic resonance imaging (MRI)--simple loops can induce heat injury.

To determine the mechanism of burn injury associated with magnetic resonance imaging (MRI), the induced current in the loops of a conductive lead was measured. Seven types of loops with effective areas within the range from 100 to 12 000 cm2 were made and then each loop was placed in the bore of a whole-body MR system at 0.5 T and MRI was carried out. During radio frequency (RF) irradiation, an induced voltage was observed in loops that were placed with their axes parallel to the linearly polarized transmitting RF field. The voltage had a sincfunction characteristic and was within the range 55-235 V at the RF pulse sequence for usual MR imaging. When the axis was vertical, negligible current was observed. A resistor inserted into the circuit of a 30 x 40 cm loop sparked and burned out. Simple loops of conductive material may result in the induction of a large and potentially hazardous voltage in the imaging system. Self-resonance of such a loop may add greatly to hazards by increasing the effective coupling to the RF transmitter. Also, impedance matching of the inserted resistor with the impedance of the loop increases the dissipated power at the resistor.

Burns, Electric↗

PubMed2001

Apoptosis, rather than oncosis, is the predominant mode of spontaneous death of isolated adult rat cardiac myocytes in culture.

A number of isolated adult cardiomyocytes dies within a few days of culture and the mode of death has recently been suggested to be apoptosis, based on its association with the appearance of DNA fragmentation. However, morphological evidence is still lacking and precise analysis, including quantification, has not been performed. Adult rat ventricular cardiomyocytes isolated by enzymatic dissociation were incubated for 7 days in a serum-free medium (the rapid attachment model) and after various incubation periods, both attached and floating cells were counted and classified based on combined criteria of morphology and membrane permeability (dye exclusion): type 1, rod cells with intact membranes; type 2, non-rod cells with intact membranes; and type 3, non-rod cells with ruptured membranes. The number of both rod-shaped and dye-excluding cells decreased with the incubation period. After 7 days culture, the number of residual cells decreased to 12% of the initial value. Electron microscopy identified type 1 cells as viable, type 2 cells as viable or apoptotic, and type 3 as undergoing oncosis (primary necrosis) or secondary post-apoptotic necrosis. Ultrastructural morphometry revealed that oncotic cell death occurred predominantly during the early phase of culture whereas the more abundant apoptotic cell death occurred throughout the culture period. In conclusion, although both apoptotic and oncotic death occur in the natural course of adult rat cardiomyocytes in short-term culture, apoptosis is more predominant. Because of the high incidence of spontaneous cell death predominantly via apoptosis, this information is important for the interpretation of studies using this cell type in culture.

Animals↗

PubMed2001

The Nd-YAG laser is useful in prevention of dental caries during orthodontic treatment.

Plaque control during the course of orthodontic treatment is not an easy task, and dental caries are not an unlikely complication. We examined the possibility of controlling dental caries with Nd-YAG laser irradiation in orthodontic patients. As a preliminary experiment, we used the Nd-YAG laser to irradiate an extracted tooth and then left it to soak in lactic acid. The decay of the tooth was evaluated with a scanning electron microscope (SEM); tooth decay was inhibited by the action of the laser. Twenty patients undergoing orthodontic treatment for early decalcification of the teeth (white spot lesions) were selected, and photographs were taken of their oral cavities. White spot lesions on the four incisors and two canines of the maxilla were traced on tracing paper, and their areas were calculated by computer. Ten of the patients received laser treatment and acidulated phosphate fluoride solution (APF); the other ten acted as the control group. Between 11 and 12 months later, we photographed the oral cavity as we had previously; the white spot lesions were again traced and their areas calculated. The changes in the areas of the white spots of the laser-irradiated and control groups showed the following increases: laser-irradiated group, 1.41 times; controls, 2.87 times. The difference was statistically significant. These results demonstrate that Nd-YAG laser irradiation with application of APF acts as an effective method of caries control during orthodontic treatment.

Acidulated Phosphate Fluoride↗

PubMed2001

[Radiation therapy for head and neck cancer].

Radiation therapy is the first choice of treatment for most of the early squamous cell carcinoma of the head and neck. Conventional radiotherapy however, contributes to the high local control rates only for carcinoma of the glottic larynx and the nasopharynx. Squamous cell carcinoma of the other sites cannot be sterilized easily only by external beam radiation therapy alone. Chemoradiotherapy, conformal three-dimensional radiotherapy and multi-daily fractionation are introduced clinically to improve local control and/or survival for radioresistant tumor. In this review, consensus report of radiation therapy for carcinoma of the larynx and pharynx, which was reached an agreement in JASTRO meeting in 1998, is introduced. The role of radiation therapy in the management of head and neck cancer in present and near future is also discussed.

Carcinoma, Squamous Cell↗

PubMed2001

[Gastrointestinal bleeding from capillary hemangioma of the ileum detected by 99mTc-HSAD scintigraphy].

It has been well-known that technetium-99m-human serum albumin-diethylenetriaminepenta-acetic acid (99mTc-HSAD) scintigraphy is useful for diagnosis of the localization of the gastrointestinal arterial or venous bleeding. In this report, we describe a case of venous bleeding from capillary hemangioma of the ileum end detected by 99mTc-HSAD scintigraphy. This patient was a 9-year-old girl with severe anemia. Gastrointestinal bleeding was suspected from her clinical course and laboratory tests. Immediately after melena occurred, 99mTc-HSAD scintigraphy showed the extravasation of RI suggesting gastrointestinal bleeding in the ileum end. Abdominal angiography immediately after 99mTc-HSAD scintigraphy, however, could not show the extravasation of contrast agent. Because the condition of the patient became worse, laparotomy was performed on the basis of 99mTc-HSAD scintigraphy findings. At surgery, venous bleeding from capillary hemangioma in the ileum end was observed. It was suggested that 99mTc-HSAD scintigraphy was very useful for identifying the gastrointestinal venous bleeding.

Child↗

PubMed2001

[Clinical evaluation of "Takotsubo" cardiomyopathy with 123I-MIBG myocardial scintigraphy: a case report].

We report a case of "Takotsubo" cardiomyopathy that was considered to be caused by hypercatecholaminemia due to mental stress. Myocardial scintigraphy using 123I-MIBG revealed severe damage to the myocardial sympathetic nerve terminals at the site of reduced left ventricular wall motion on left ventriculography. In this case, cardiac nuclear imaging with 123I-MIBG appeared to be useful for understanding the pathophysiology when combined with ECG and left ventriculography.

3-Iodobenzylguanidine↗

PubMed2000

Bioactivation of diesel exhaust particle extracts and their major nitrated polycyclic aromatic hydrocarbon components, 1-nitropyrene and dinitropyrenes, by human cytochromes P450 1A1, 1A2, and 1B1.

The genotoxicities of four samples of diesel exhaust particle (DEP) extracts (DEPE) and nine nitroarenes found in DEPE were investigated after activation catalyzed by human cytochrome P450 (P450) family 1 enzymes co-expressed with NADPH-cytochrome P450 reductase (NPR) in Escherichia coli membranes. The DEPE samples induced umu gene expression in Salmonella typhimurium TA1535/pSK1002 without any P450 system and were further activated by human P450 1B1/NPR membranes. Moderate activation of the DEPE sample by P450 1A2/NPR membranes was also observed, but not by either P450 1A1/NPR or NPR membranes. 1-Nitropyrene (1-NP) was strongly activated by human P450 1B1/NPR membranes. 1,8-Dinitropyrene (1,8-DNP) was most highly activated by P450 1A1 and 1B1 systems for the three DNPs tested. In contrast, 1, 3-DNP was inactivated by P450 1A1/NPR, 1A2/NPR, and 1B1/NPR systems and slightly activated by NPR membranes. 2-Nitrofluoranthene (2-NF) and 3-nitrofluoranthene (3-NF) showed activities similar to 1-NP after bioactivation by P450 1B1/NPR membranes. However, the genotoxicities of 6-nitrochrysene, 7-nitrobenz[a]anthracene, and 6-nitrobenzo[a]pyrene were all weak in the present assay system. Apparent genotoxic activities of DEPE were very low compared with standard nitroarenes in the presence of P450s, possibly because unknown component(s) of DEPE had inhibitory effects on the bioactivation of 1-NP and 1,8-DNP catalyzed by human P450 1B1. These results suggest that environmental chemicals existing in airborne DEP, in addition to 1-NP, 1,6-DNP, 1,8-DNP, 2-NF, and 3-NF, can be activated by human P450 1B1. Biological actions of air pollutants such as nitroarenes to human extrahepatic tissues may be of concern in tissues in which P450 1B1 is expressed.

Aryl Hydrocarbon Hydroxylases↗

PubMed2000

Tyrosinase family proteins are antigens specific to Vogt-Koyanagi-Harada disease.

Vogt-Koyanagi-Harada (VKH) disease (and sympathetic ophthalmia) is an ocular inflammatory disease that is considered to be a cell-mediated autoimmune disease against melanocytes. The purpose of this study was to determine the Ags specific to VKH disease and to develop an animal model of VKH disease. We found that exposure of lymphocytes from patients with VKH disease to peptides (30-mer) derived from the tyrosinase family proteins led to significant proliferation of the lymphocytes. Immunization of these peptides into pigmented rats induced ocular and extraocular changes that highly resembled human VKH disease, and we suggest that an experimental VKH disease was induced in these rats. We conclude that VKH disease is an autoimmune disease against the tyrosinase family proteins.

Adult↗

PubMed2000

The 1.9 A resolution structure of phospho-serine 46 HPr from Enterococcus faecalis.

The histidine-containing phosphocarrier protein HPr is a central component of the phosphoenolpyruvate:sugar phosphotransferase system (PTS), which transfers metabolic carbohydrates across the cell membrane in many bacterial species. In Gram-positive bacteria, phosphorylation of HPr at conserved serine 46 (P-Ser-HPr) plays several regulatory roles within the cell; the major regulatory effect of P-Ser-HPr is its inability to act as a phosphocarrier substrate in the enzyme I reaction of the PTS. In order to investigate the structural nature of HPr regulation by phosphorylation at Ser46, the structure of the P-Ser-HPr from the Gram- positive bacterium Enterococcus faecalis has been determined. X-ray diffraction analysis of P-Ser-HPr crystals provided 10,043 unique reflections, with a 95.1 % completeness of data to 1.9 A resolution. The structure was solved using molecular replacement, with two P-Ser-HPr molecules present in the asymmetric unit. The final R-value and R(Free) are 0.178 and 0.239, respectively. The overall tertiary structure of P-Ser-HPr is that of other HPr structures. However the active site in both P-Ser-HPr molecules was found to be in the "open" conformation. Ala16 of both molecules were observed to be in a state of torsional strain, similar to that seen in the structure of the native HPr from E. faecalis. Regulatory phosphorylation at Ser46 does not induce large structural changes to the HPr molecule. The B-helix was observed to be slightly lengthened as a result of Ser46 phosphorylation. Also, the water mediated Met51-His15 interaction is maintained, again similar to that of the native E. faecalis HPr. The major structural, and thus regulatory, effect of phosphorylation at Ser46 is disruption of the hydrophobic interactions between EI and HPr, in particular the electrostatic repulsion between the phosphoryl group on Ser46 and Glu84 of EI and the prevention of a potential interaction of Met48 with a hydrophobic pocket of EI.

Bacterial Proteins↗

PubMed2000

On the tryptophan residue of smooth muscle myosin that responds to binding of nucleotide.

Initially, we asked which (of 10) smooth muscle myosin head residues responds to MgADP or MgATP binding with enhanced fluorescence emission (Trp-441 and Trp-512 were leading candidates)? To decide, we prepared sham-mutated smooth muscle heavy meromyosin (HMM), W441F HMM, and W512F HMM. On adding MgATP, emission of wild-type and W441F HMMs increased by 25-27%, but that of W512F HMM by 5%. So, in myosin, 512 is the "sensitive Trp." Unexpectedly, properties of W512F HMM [elevated Ca(2+)-ATPase, depressed EDTA (K(+))-ATPase, no regulation of its basal or actin-activated Mg(2+)-ATPase by phosphorylation of its "regulatory" light chain, limited actin activation, and inability to move actin filaments in a motility assay] are strikingly like those of smooth muscle myosin reacted at Cys-717 with thiol reagent. From crystallography-based [Houdusse, A., Kalabakis, V. N., Himmel, D., Szent-Györgyi, A. G. & Cohen, C. (1999) Cell 97, 459-470] simulations, we found that in wild-type HMM with MgADP added, Trp-512 is in a "hydrophobic pocket," but that pocket becomes distorted in W512F HMM. We think that there is a "path of influence" from 512 to 717 to the active site. We suggest that the mutational changes at 512 are transmitted along this path to Cys-717, where they induce changes similar to those caused by reacting wild-type HMM with thiol reagent.

Adenosine Diphosphate↗

PubMed2000

Clinical Results of Selective Laser Trabeculoplasty.

Purpose: Selective laser trabeculoplasty (SLT) is a new technique aimed to developed to impact pigmented trabecular cells selectively. Compared with ordinary argon laser trabeculoplasty, it is expected to have fewer complications with more efficacy for open-angle glaucoma. In this study we performed SLT on 17 eyes of 10 patients with primary open-angle glaucoma and 1 eye with capsular glaucoma.Methods: Follow-up period was up to 10 months. Average energy irrachieted was 28.14 mJ (0.47 mJ x 59 spots) against pigmented trabecular band over the half circumference of anterior chamber angle.Results: Preoperative mean intraocular pressure (IOP) was 22.8 mmHg and postoperative mean IOP was decreased significantly to 8.6, 17.3, and 16.1 mmHg at 1, 3, and 6 months after treatment, respectively. The average maximum IOP reduction was 8.8 (3 approximately 1 8) mmHg after SLT. Among 11 eyes showing transient IOP elevation, 6 eyes had an elevation of more than 6 mmHg. No remarkable postoperative complications were noted.Conclusion: SLT is a safe and effective modality for the treatment of open-angle glaucoma such as primary open-angle glaucoma (POAG) and capsular glaucoma.

Journal Article↗

PubMed2000

Crystal structure of Pseudomonas aeruginosa PAK pilin suggests a main-chain-dominated mode of receptor binding.

Fibers of pilin monomers (pili) form the dominant adhesin of Pseudomonas aeruginosa, and they play an important role in infections by this opportunistic bacterial pathogen. Blocking adhesion is therefore a target for vaccine development. The receptor-binding site is located in a C-terminal disulphide-bonded loop of each pilin monomer, but functional binding sites are displayed only at the tip of the pilus. A factor complicating vaccination is that different bacterial strains produce distinct, and sometimes highly divergent, pilin variants. It is surprising that all strains still appear to bind a common receptor, asialo-GM1. Here, we present the 1.63 A crystal structure of pilin from P. aeruginosa strain PAK. The structure shows that the proposed receptor-binding site is formed by two beta-turns that create a surface dominated by main-chain atoms. Receptor specificity could therefore be maintained, whilst allowing side-chain variation, if the main-chain conformation is conserved. The location of the binding site relative to the proposed packing of the pilus fiber raises new issues and suggests that the current fiber model may have to be reconsidered. Finally, the structure of the C-terminal disulphide-bonded loop will provide the template for the structure-based design of a consensus sequence vaccine.

Amino Acid Sequence↗

PubMed2000

Determination of saccharides in sake by high-performance liquid chromatography with polarized photometric detection.

A high-performance liquid chromatographic method has been developed for the determination of saccharides in sake, an alcoholic beverage brewed from rice. Saccharides in sake were separated on a normal phase (carbamoyl bonded silica) column using a linear gradient elution of water in acetonitrile. Seven saccharides, glucose, maltose, isomaltose, maltotriose, panose, isomaltotriose and ethyl alpha-D-glucoside, were determined by a polarized photometric detector. Unidentified peaks suggesting saccharides with polymerization degrees over 4 were also observed. The proposed method did not require any sample clean-up treatment. As an application, saccharide compositions in various kinds of sake were compared.

Beverages↗