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Biomedical subjects

K Miyata

Publications and source records attributed to K Miyata.

At least 109 records · Page 6Linked to original sources
PubMed1999

[Characteristics of the clients in a geriatric intermediate care facility located in the suburbs of an urban area and factors related to the discharge destinations desired by family caregivers].

Among the clients in a geriatric intermediate care facility located in the suburbs of Osaka and their family caregivers (72 subjects), the characteristics of the clients and their caregivers, and the discharge destination desired by their family caregivers were investigated, and the associated factors were evaluated. 1. Characteristics of the clients. The clients were elderly females with a low degree of independence, and dementia was observed in about 60% of them. The clients had a relatively large number of children, but many of them lived alone before admission. The rate of admission from hospitals was high (54%), and that of discharge to hospitals was also high (50%). Sixty-seven percent of the clients stayed for a long duration of over 6 months. 2. Conditions of the family caregivers. Most of the family caregivers were daughters or daughters-in-law, and considered themselves to be healthy. Sixty-three percent of the caregivers had jobs. However, most of the caregivers did not have sub-caregiver. 3. Factors related to the discharge destination desired by family caregivers. Not many family caregivers (19.4%) wanted them to go back to their homes after discharge, but their preferred discharge destinations were home (19.4%), hospitals (55.5%), and nursing homes (25.1%). The caregivers of single household clients often desired a nursing home as the discharge destination, and those of the clients from a 2- or 3-generation household often desired a hospital. The factors related to the discharge destination desired by client's family caregivers were that the client not show dementia, the job of the caregiver was a part-time job, there was a sub-caregiver, and the client had the experience of home public health nursing visits. This study showed, the percentage of the clients discharged from the geriatric intermediate care facility to their homes was low, and that of the family caregivers who desired their home as the discharge destination was also low. However, the results suggested that leading the discharge destination to the client's home is possible if social resources are provided such as the use of public health nursing services.

Aged↗
PubMed1999

Novel small molecule nonpeptide aminopeptidase n inhibitors with a cyclic imide skeleton.

A novel series of small molecule nonpeptide aminopeptidase N (APN) inhibitors with a N-phenylphthalimide or N-phenylhomophthalimide skeleton were prepared. Evaluation of their protease inhibitory activities revealed that (i) some N-phenylphthalimide analogs are potent APN inhibitors, but they are also inhibitors of another protease, dipeptidylpeptidase IV (DPP-IV), and (ii) some N-phenylhomophthalimide analogs, including 2-(2,6-diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (PIQ-22), are potent and specific inhibitors of APN without DPP-IV-inhibitory activity. The structure-activity relationship studies of N-phenylphthalimides and N-phenylhomophthalimides are reviewed. PIQ-22 showed potent tumor-cell invasion-inhibitory activity.

Antineoplastic Agents↗
PubMed1999

Hyaluronan synthase expression in bovine eyes.

PURPOSE: Hyaluronan (HA), a high-molecular-weight linear glycosaminoglycan, is a component of the extracellular matrix (ECM). It is expressed in eyes and plays important roles in many biologic processes, including cell migration, proliferation, and differentiation. Hyaluronan is produced by HA synthase (HAS), which has three isoforms: HAS1, HAS2, and HAS3. In this study, the HAS expression in the anterior segment of bovine eyes was investigated to determine the significance of HA in eyes. METHODS: To obtain bovine HAS probes, degenerate oligonucleotide primers, based on well-conserved amino acid sequences including the catalytic region of each HAS isoform, were used for reverse transcription-polymerase chain reaction to amplify mRNA from bovine corneal endothelial cells (BCECs). Hyaluronan synthase-1 expression in the anterior segment of bovine eyes at the protein level was investigated by immunohistochemistry. RESULTS: All three HAS isoforms were expressed in BCECs at the mRNA level. Amplified cDNA fragments of HAS1, HAS2, and HAS3 from BCECs can be aligned to human counterparts, showing similarities of 100%, 97.3%, and 100%, respectively, at the amino acid level. Hyaluronan synthase 1 was expressed at the protein level in corneal epithelium, keratocyte, corneal endothelium, conjunctival epithelium, ciliary epithelium, capillary endothelium, and trabecular meshwork. CONCLUSIONS: Hyaluronan synthase isoforms were expressed in the ocular anterior segment and are speculated to be involved in HA production in situ.

Amino Acid Sequence↗
PubMed1999

[A case report of systemic lupus erythematosus patient with severe lupus retinopathy and antiphospholipid antibody].

An eleven-year-old boy with systemic lupus erythematosus (SLE) developed severe bilateral lupus retinopathy when he was in active stage of SLE. The patient, who had suffered from SLE for 3 years, was admitted to our hospital because of high grade fever, systemic lymphadenopathy, leukopenia, elevation of erythrocyte sedimentation rate and hypocomplementemia. The dose of prednisolone was increased considering he was exacerbated of SLE, however, the convulsion as CNS lupus occurred to him. After the event he noted loss of vision in his bilateral eyes. The ophthalmologic examination revealed the lesions of cotton-wool spots, retinal vessel dilatations and diffuse occlusions of the retinal arterioles and venules which were compatible with lupus retinopathy. Although the coagulation time was normal, antiphospholipid antibodies were positive at the time of ocular involvement. Careful attention should be paid to the occurrence of lupus retinopathy when the patients with SLE developed in the active stage or CNS lupus, especially they have antiphospholipid antibodies.

Antibodies, Antiphospholipid↗
PubMed1999

Effects of lipid mediator antagonists on predominant mediator-controlled asthmatic reactions in passively sensitized guinea pigs.

The role of cysteinyl leukotrienes (cys-LTs) and thromboxane A(2) (TXA(2)) in guinea pig models of aspects of bronchial asthma was investigated. In a novel antigen (BSA)-induced asthmatic model using passively sensitized guinea pigs, pretreatment with varying doses of indomethacin controlled the ratio of followed lipid mediators, LTC(4)/D(4)/E(4) and TXB(2), in lungs of challenged guinea pigs. The predominant mediator in indomethacin-untreated asthma was TXA(2), and complete inhibition of cyclooxygenase by i.v. injection of 5-mg/kg indomethacin-induced cys-LTs mainly mediated asthmatic response. Furthermore, a 1-mg/kg indomethacin dose induced an asthmatic state where both cys-LTs and TXA(2) equally participated. Either LTD(4) or TXA(2) receptor antagonists given alone inhibited the asthmatic response in conditions where the corresponding mediator plays a predominant role. The combination of LTD(4) and TXA(2) receptor antagonists exhibited significant effects irrespective of the condition used. Under conditions where both mediators equally participate, a combination of both receptor antagonists showed additive inhibition. YM158, a newly synthesized and orally active dual antagonist for LTD(4) and TXA(2) receptors, showed the same antiasthmatic effect as a combinated LTD(4) receptor antagonist and a TXA(2) receptor antagonist mixture. Therefore, broad-acting compounds such as YM158 are expected to have antiasthmatic efficacies in a broader class of asthmatic patients than single-acting drugs.

Administration, Oral↗
PubMed1999

[Short interval change of 99mTc-ethyl cysteinate dimer single photon emission computed tomography in Wilson's disease].

We studied short interval change of cranial computed tomography (CT), magnetic resonance imaging (MRI) and 99mTc-ethyl cysteinate dimer single photon emission computed tomography (99mTc-ECD SPECT) in a case of Wilson's disease. Before treatment, CT scan showed low density changes in the bilateral thalamus and basal ganglia, and MRI demonstrated high intensity in same lesions. 99mTc-ECD SPECT study revealed a hypoperfusion in bilateral thalamus. After 2 months under D-penicillamine therapy, neurological findings had improvement. Hypoperfusion in the thalamus with 99mTc-ECD SPECT significantly improved, whereas abnormal findings of CT scan and MRI persisted. 99mTc-ECD SPECT study may be useful for the planning of the treatment of Wilson's disease.

Adolescent↗
PubMed1999

Increased circulating vascular endothelial growth factor is correlated with disease activity in polyarticular juvenile rheumatoid arthritis.

OBJECTIVE: To investigate the relevance of vascular endothelial growth factor (VEGF) in the pathogenesis of juvenile rheumatoid arthritis (JRA). METHODS: Serum VEGF levels in 58 patients with JRA (systemic in 17, polyarticular in 29, pauciarticular in 12) were measured by ELISA and compared with those of 21 patients with infectious diseases and 50 healthy children. Correlations of VEGF levels with number of joints with active arthritis, erythrocyte sedimentation rate (ESR), and hyaluronic acid (HA) were examined. RESULTS: Serum levels of VEGF in patients with JRA were significantly higher than in healthy controls. Patients with systemic and polyarticular JRA showed statistically higher levels of VEGF than those with infectious diseases. VEGF levels correlated statistically with C-reactive protein (CRP) in patients with both infectious diseases and polyarticular JRA, but the regression slope (VEGF/CRP) was much steeper in polyarticular JRA than in infectious diseases. Serum VEGF levels correlated with disease activity variables such as the number of joints with active arthritis, ESR, and serum HA levels in polyarticular JRA. CONCLUSION: The correlation of serum VEGF levels and disease activity in polyarticular JRA suggests that VEGF may take an active part in joint inflammation.

Adolescent↗
PubMed1998

Binding of YM158, a new dual antagonist for leukotriene D4 and thromboxane A2 receptors, to guinea pig lung membranes.

Arachidonic acid metabolites mediate inflammatory responses at a cellular level. The affinity of the newly synthesized compound YM158, 3-[(4-tert-butylthiazol-2-yl)methoxy]-5'-[3-(4-chlorobenzenesuf onyl)propyl-2'-(1H-tetrazol-5-ylmethoxy)benzanilide monosodium salt monohydrate, for leukotriene D4 and thromboxane A2 receptors was examined in radioligand binding assays. YM158 inhibited [3H]leukotriene D4 and [3H]U46619 (9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F2alpha) binding to guinea pig lung membrane preparations, with Ki values of 0.64+/-0.06 nM for leukotriene D4 and 5.0+/-0.88 nM for thromboxane A2 receptors. The Hill coefficients (nH) did not significantly differ from unity, indicating that this antagonism is competitive. In contrast, YM158 showed no affinity for several other receptors, including neurotransmitter-related (alpha1-, alpha2-, beta-adrenoceptors, histamine, 5-HT, muscarinic, sigma), C5a, opioid, Ca2+ channel, K+ channel, protein kinase C, bradykinin, endothelin, neurokinin and platelet activating factor receptors. These studies indicate that YM158 is a highly selective dual antagonist for leukotriene D4 and thromboxane A2 receptors, and this has potential clinical and research applications.

Animals↗
PubMed1998

Study on urine boron reference values of Japanese men: use of confidence intervals as an indicator of exposure to boron compounds.

A simple and rapid method for the determination of urine boron by inductively-coupled plasma argon emission spectrometry (ICPAES) has been developed to establish boron exposure guidelines. After 11-fold dilution in 18.25 M omega cm ultra-pure water and vigorous shaking, urine may be directly injected into the spectrometer, providing accurate and reproducible results. We report the results obtained with urine samples obtained from a group of male Japanese electronic workers (n = 102) who had not been exposed to boron; boron concentrations were corrected with use of a specific gravity of 1.024 g/ml. The frequency distribution resulted in a log-normal distribution diagram for anatomical spread. The geometric mean values for urine boron in the non-exposed workers was 798.0 micrograms/l, while the confidence interval (C.I.) was between 398.1 and 1599.6 micrograms/l. Taking into consideration the short biological half-life of boron and its major excretion route via urine, urine was considered to be a suitable means for monitoring of exposure to this element. We conclude that the guidelines established by determining boron reference values are useful for the protection of individuals exposed to boron in their working environments.

Adult↗
PubMed1998

Direct transfer of bovine embryos frozen-thawed in the presence of propylene glycol or ethylene glycol under on-farm conditions in an integrated embryo transfer program.

An integrated bovine embryo transfer program was conducted in collaboration with 11 Japanese prefectural livestock experiment stations. The program was conducted to evaluate the practicability of the direct transfer method for bovine embryos frozen-thawed in the presence of propylene glycol (PG) or ethylene glycol (EG) under on-farm conditions. Embryos at the compacted morula to expanded blastocyst stages were collected from superovulated donors on Day 7 or 8 after estrus and equilibrated in 1.6 M PG or 1.8 M EG in Dulbecco's phosphate-buffered saline (DPBS) supplemented with 20% heat-inactivated calf serum. Embryos were then loaded individually into a 0.25-ml straw and placed directly into a cooling chamber of a programmable freezer precooled to -7 degrees C. After 2 min, the straw was seeded, maintained at -7 degrees C for 8 min more, and then cooled to -30 degrees C either at 0.3 degree C/min or 0.5 degree C/min before being plunged into liquid nitrogen. Embryos at the same stages were also frozen in the presence of 1.4 M glycerol (GLY) by a conventional method, which served as a control. The frozen embryos were thawed by allowing the straws to stand in air for 5 to 10 sec and then immersing them in a 30 degrees C water bath. Embryos frozen-thawed in the presence of PG or EG were nonsurgically transferred into the uterine horn without diluting the cryoprotectant. Embryos frozen-thawed in the presence of GLY were nonsurgically transferred after removing GLY either by the stepwise method (GLY-I) or by in situ dilution with 0.3 M sucrose solution (GLY-II). A total of 1,273 (PG: 400, EG: 418, GLY-I: 177, GLY-II; 278) frozen-thawed embryos was transferred into recipients, yielding 545 pregnancies (overall: 42.8%, PG: 36.0%, EG; 44.7%, GLY-I; 48.6%, GLY-II; 46.0%). The pregnancy rate with PG was significantly lower than that with EG or GLY-II (P < 0.05). The pregnancy rate was affected by the type of cryoprotectant, the region where the embryo transfer program was carried out, the developmental stage of the embryos, the parity of the recipients, and corpus luteum (CL) quality of the recipients. There were no differences in rates of abortion and stillbirth among the 3 cryoprotectants. The present study demonstrates that EG can be effectively used as a cryoprotectant for freezing and direct transfer of bovine embryos, and that the direct transfer method is applicable under on-farm conditions.

Animals↗
PubMed1998

A novel human tumor necrosis factor alfa mutein, F4614, inhibits in vitro and in vivo growth of murine and human hepatoma: implication for immunotherapy of human hepatocellular carcinoma.

Although treatment for hepatocellular carcinoma (HCC) has recently improved, most patients still relapse and die from this disease. The development of new therapeutic and preventive strategies for HCC is, therefore, required. A novel mutant protein (mutein) of human tumor necrosis factor alfa (TNF-alpha mutein F4614, 1SSSRGDSD... 29V ... 155L) was developed to decrease several adverse effects of TNF-alpha. F4614 is known to lack hypotensive effects of human TNF-alpha without losing its anti-tumor effect in mice transplanted with Meth-A sarcoma. Our study investigated the anti-tumor effects of F4614 against hepatoma cells in vitro and in vivo. F4614 significantly inhibited growth of all four tumor cells in vitro. A murine hepatoma cell line, MH134, when incubated in the presence of F4614, exhibited upregulation of surface major histocompatibility complex (MHC) class-I, intercellular adhesion molecule-1 (ICAM-1) and B7-1 molecules, and a decreased proportion of cells in the G2/M phase of the cell cycle. In addition, F4614 induced apoptosis in a significant number of MH134 cells. TNF-alpha and F4614 (5 microg/mouse daily for 5 days) showed similar anti-tumor activities in syngeneic MH134-bearing mice and heterogeneic PLC/PRF/5-bearing athymic nude mice. Intratumoral injection of F4614 or TNF-alpha was more effective than intravenous injection. Immunohistochemical analysis of the tumors treated by F4614 revealed that tumors were surrounded with a large number of Mac-1+ cells and a small number of CD4+ and CD8+ T cells; that suggests that intratumoral injection of F4614 elicited host immunoreactions. Thus, F4614 may be a new strategy for immunotherapy of HCC.

Animals↗
PubMed1998

Protective effect of the combined treatment of pancreatic and neutrophil elastase inhibitors on acute pancreatitis elicited by lipopolysaccharide in rats given intraductal injection of taurocholate plus trypsin.

A severe acute pancreatitis was produced by intraperitoneal injection of lipopolysaccharide (LPS) in rats with preexisting hemorrhagic and necrotizing pancreatitis induced by retrograde injection of a 5% taurocholate plus 1% trypsin solution into the pancreatic duct. Mortality and time-course changes in pancreatic, hepatic, renal and pulmonary functions, and organ myeloperoxidase (MPO) levels were examined in this model. LPS at an intraperitoneal dose of 30 mg/kg, which scarcely caused death and had no marked effect on serum parameters and organ MPO levels in rats without pancreatitis, increased the mortality in rats with taurocholate plus trypsin-induced pancreatitis. Pancreatic weight and ascitic volume increased in rats with taurocholate plus trypsin-induced pancreatitis regardless of the presence or absence of LPS. Serum amylase and lipase levels were also significantly increased in rats with induced pancreatitis, but was higher in the group given LPS. Serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN) and creatinine levels were significantly elevated in LPS-treated rats with induced pancreatitis, whereas levels in rats with induced pancreatitis not given LPS were only slightly elevated. Renal weight was also significantly increased in rats with induced pancreatitis despite the presence or absence of LPS. In LPS-treated rats with induced pancreatitis, the arterial oxygen pressure, pulmonary weight and pulmonary MPO level were significantly elevated. However, the MPO level in the kidney in these rats was not different from that in control rats, indicating that the renal dysfunction was not produced by the infiltration of neutrophils into the kidney. Increase in the pancreatic MPO level was observed in rats with induced pancreatitis, but combination treatment with LPS did not raise it. Protective effects of prophylactic treatment of 2-(3-methylsulfonylamino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-( 3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide (compound 1), a neutrophil elastase inhibitor, and trifluoroacetyl-L-lysyl-L-alaninanilide hydrochloride (compound 2), a pancreatic elastase inhibitor, on mortality were also examined in this model. Results were compared with that of the combined treatment of compound 1 and compound 2. In LPS-treated rats with taurocholate plus trypsin-induced pancreatitis, the combined treatment of compound 1 (2 mg/kg/h) and compound 2 (30 mg/kg/h) significantly reduced mortality, whereas single treatment of compound 1 or compound 2 did not show the beneficial effect. These results suggest that marked hepatic and renal dysfunction accompanies pancreatitis in this pancreatitis model rats, which may be good models for acute pancreatitis in humans. It is also suggested that neutrophil and pancreatic elastases may be synergistically involved in the pathogenesis of acute pancreatitis in this model.

Animals↗
PubMed1998

Protective effects of a PAF receptor antagonist and a neutrophil elastase inhibitor on multiple organ failure induced by cerulein plus lipopolysaccharide in rats.

The inhibitory effects of YM264, a selective platelet activating factor (PAF) receptor antagonist, and 2-(3-methylsulfonylamino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-( 3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide (compound 1), a neutrophil elastase inhibitor, on mortality, and pancreatic, hepatic, renal and pulmonary dysfunction were evaluated in a rat model of multiple organ failure (MOF) accompanying acute pancreatitis. MOF was produced by intraperitoneal injection of lipopolysaccharide (LPS, 30 mg/kg) in rats with cerulein-induced pancreatitis. LPS dose-dependently increased the mortality in rats with or without pancreatitis. The threshold dose which produced death in rats without pancreatitis was 30 mg/kg. This same dose evoked death in more than 40% of rats with pancreatitis. Time-course changes in serum enzyme and organ myeloperoxidase (MPO) levels were first examined in rats with induced MOF, and the results were compared with those in rats treated with only LPS or cerulein. Pancreatic weight, and serum amylase and lipase levels significantly increased in rats with cerulein-induced pancreatitis despite the presence or absence of LPS, but recovery of these pancreatic dysfunctions was slower in the group given LPS. However, serum GOT, GPT, BUN and creatinine levels were significantly elevated only in MOF rats. In the MOF rats, the MPO level in the lung was significantly elevated and arterial oxygen pressure was decreased, indicating that infiltration of neutrophils into the lung might be involved in pulmonary dysfunction. However, the MPO levels in the pancreas and kidney in the MOF rats were not remarkably different from those in normal rats. The inhibitory effects of YM264 and compound 1 on mortality and organ dysfunction were examined in this MOF model. The 24-h survival rate for rats prophylactically and therapeutically treated with an intravenous infusion of YM264 at 0.1 mg/kg h was significantly higher than that of controls. The 24-h survival rate for rats treated prophylactically by intravenous infusion of 2 mg/kg h of compound 1 was significantly higher than that of control, whereas a beneficial dose of compound 1 was 5 mg/kg h in therapeutically treated rats. Prophylactic treatment with YM264 (0.1 mg/kg h) and compound 1 (2 mg/kg h) ameliorated organ dysfunction in rats with MOF. In conclusion, pancreatic, hepatic, renal and pulmonary dysfunctions are observed in this rat MOF model. The PAF receptor antagonist and neutrophil elastase inhibitor reduce the mortality rate in rats with MOF due to their inhibitory effects on organ dysfunction, indicating that PAF and neutrophil elastase may play important roles in the development of MOF. These results in the present model are largely consistent with those in patients with MOF, indicating that this model is suited for MOF in humans and may be used as a model to test new therapeutic approaches.

Alanine Transaminase↗
PubMed1998

Urinary biomarkers monitoring for experimental fluoride nephrotoxicity.

An excess of sodium fluoride (135 mg F/kg body weight) was given in a single oral dose to male Wistar rats. Effects were investigated of fluoride-induced acute kidney intoxication on the time-dependent variations of urine volume. Also, of urinary fluoride ion (F-), alpha-glutathione-S-transferase (alpha-GST), N-acetyl-beta-D-glucosaminidase (NAG), and creatinine (CR) concentrations. Fluoride administration strongly affects these urinary biochemical indices. Of the several biomarkers studied, alpha-GST is particularly useful as marker of S3 proximal tubule damage. We found that alpha-GST shows the strongest and more durable changes as a result of the large dose of F- given to the experimental animals. Our results suggest that the toxic effect of F- on the kidney may be more pronounced in the proximal tubule than the glomeruli region, and that the disorder of the proximal tubule is more serious in the S3 segment than S1 or S2 segment. Alpha-GST proved to be a useful marker for the early detection and long-term observation of proximal renal tubular injury resulting from F- intoxication. The animal model should help to establish guidelines for the treatment of industrial workers suffering from acute renal failure resulting from accidental exposure to fluoride.

Acetylglucosaminidase↗
PubMed1998

Twenty-five types of T-cell receptor Vbeta family repertoire in patients with Kawasaki syndrome.

UNLABELLED: Recently, a possible relationship between Kawasaki syndrome (KS) and superantigen has been discussed since the report of selective expansion of specific Vbeta family in the acute phase of KS. To further investigate the relationship between KS and superantigens, we examined 25 types of T-cell receptor Vbeta family repertoire in patients with KS using the reverse transcription polymerase chain reaction. This is the first attempt to examine all of 25 Vbeta families in KS. A non radioisotope method was used to quantify mRNA so that the experiment was safer, simpler, and faster. An expression index (EI) for each Vbeta was defined as: (the amount of each Vbeta mRNA)/(the sum of all Vbeta mRNA) x 100. Ten patients with KS and ten normal children were studied. The Vbeta9 and Vbeta15 of acute phase of KS showed both significantly lower mean EI and significantly higher frequency of a decreased EI value as compared with control children. Selective expansion of the Vbeta family in the patients with KS was not observed. Although highly increased EIs were observed in various Vbetas, their frequency was not statistically significant. The pattern of increased Vbetas did not show the specific pattern that indicates a particular superantigen. CONCLUSION: In Kawasaki syndrome non-radioisotope method for analysing Vbeta mRNA is useful in cases where many samples have to be handled. The depletion of Vbeta9 and Vbeta15 or highly increased expression index in the acute phase of Kawasaki syndrome might suggest a relationship to superantigens.

Bacterial Toxins↗