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Biomedical subjects

K Miyata

Publications and source records attributed to K Miyata.

At least 217 records · Page 12Linked to original sources

[A case of metamorphopsia caused by a very localized spotty infarct].

A 51-year-old woman complained that her right side of the face looked blurring and the right margin of all the objects in her visual field looked blurred. Neurological examination on admission showed no abnormalities including higher cortical function and visual fields except the metamorphopsia. In this case, a very localized spotty infarct caused no neurological symptoms other than the metamorphopsia. CT scan and MRI revealed a spotty lesion of infarct between retrosplenium and cingulate gyrus on the left side. This can be a breakthrough case to locate the exact anatomic pathology that causes metamorphopsia.

Cerebral Infarction↗

Determination of the spleen-blood partition coefficient for water with oxygen-15-water and oxygen-15-carbon dioxide dynamic PET steady-state methods.

METHODS: Regional splenic blood flow (SBF) was quantified by PET using a steady-state method with 15O-carbon dioxide. SBFs were determined using 104 tomographic planes obtained from 49 patients. RESULTS: When the spleen-blood partition coefficient for water (p) was > or = 0.85, significant correlations (p < 0.005) were found between SBF values determined by the steady-state and dynamic methods. The best correlation between SBFs determined by the two methods (r = 0.571) was found when p = 0.93. The best regression line, however, was thought to be the line when p = 0.93. The regression line between SBF calculated by the steady-state method (y) and SBF determined by the dynamic method (x) was y = 0.57 x + 0.03 with an F ratio of 48.75 (d.f. = 103, p = 5.0 x 10(-8)%, by ANOVA) when p = 0.92. CONCLUSION: A quick evaluation of SBF can be made by using the newly defined regression line.

Carbon Dioxide↗

[Quantitative analyses of glycosaminoglycans in tear fluids in normal human eyes and eyes with corneal epithelial disorders].

The existence and pathophysiological role of glycosaminoglycans in the tear fluid in humans was investigated using quantitative analyses of hyaluronic acid and chondroitin sulfate in the tear fluid. The subjects were 42 eyes of 31 normal controls, 9 eyes of 9 patients with superficial punctate keratitis (SPK), and 13 eyes of 13 patients with epithelial defect. After an instillation of 100 microliters saline solution in the conjunctival sac, as much tear fluid as possible was collected from the lower cul-de-sac. The glycosaminoglycans in the tears were then treated with chondroitinase ABC to make fractions of unsaturated disaccharides. The quantities of disaccharides were determined by high-performance liquid chromatography. Concentrations were expressed as nanomoles of unsaturated disaccharides per protein in the tears. The concentrations of hyaluronic acid and chondroitin sulfate in the normal controls were 0.07 +/- 0.12(n mol/mg protein) and 6.91 +/- 3.63 (n mol/mg protein), respectively. The mean concentration of hyaluronic acid was significantly higher in patients with epithelial erosion than in normal controls, whereas the mean concentration of chondroitin sulfate was significantly lower in patients with epithelial erosion than in normal controls. There was no significant difference in the concentration of glycosaminoglycans between the patients with SPK and normal controls. The results of our study suggest that glycosaminoglycans are synthesized and endogenously secreted into the tear fluids and, especially in the case of hyaluronic acid, may play an important role in corneal epithelial wound healing in patients with epithelial erosion.

Adult↗

[Experimental studies on influence of alignment errors on measurement in a corneal topographic system--relationship between degree of measurement error and working distance].

To evaluate the influence of alignment errors in focusing on the results of measurements in corneal topography, we experimented using polymethyl-methacrylate balls with definite radii of curvature as test objects. We used 3 different corneal topographic systems with different working distances to clarify the relationship between the degree of errors and the working distance. We determined the refractive power of the test balls by the topographic systems and studied changes in the values as the balls were slightly displaced from the alignment position axially, or horizontally. The test balls were set on the stage with a micrometer so that the distance of displacement could be determined precisely. When the test balls were placed precisely in alignment, there was no significant relationship in the magnitude of measurement errors with working distance of the topographical systems. When the test balls were displaced axially, the measurement values decreased as the balls come near from the alignment position and increased as they moved away from the alignment position. The magnitude of the measurement errors caused by back and forth displacement of the object became larger as the working distance of the topographic system became shorter. There was no specific relationship between the degree of measurement errors and the working distance when the balls were displaced horizontally.

Cornea↗

[Effects of blowing or aspiration on ablation rate by excimer laser].

Accurate calibration of ablation rate by excimer laser prerequisite for precise photorefractive keratectomy (PRK). When a polymethylmethacrylate (PMMA) plate is ablated by excimer laser, debris is generated, which may affect homogeneity of the laser beam and energy density, and change the ablation rate. In order to clarify the effects of the debris on the ablation rate, we studied the changes in the ablation rate when the debris was removed by blowing or aspirating over the ablation area during PRK.PMMA plates were ablated using a scanning excimer laser system (EC-5000, NIDEK, Japan) in PRK mode under the following conditions: (1) with air blowing over the ablation area, (2) with aspiration of the debris, and (3) without treatment. The ablation rates were determined by measuring the refractive power of PMMA plates with a lens meter. The ablated surface was observed by scanning electron microscope (SEM). The ablation rate with blowing was the highest among the three conditions, that with aspiration was the second, and that without treatment was the lowest. The ablation rates with blowing showed no significant change when the ablation rates were changed. However, the ablation rates with aspiration or without treatment decreased as the pulse rate increased. The surface ablated during blowing was the smoothest in SEM photographs. We concluded that calibration of the ablation rate using PMMA plates must be done with appropriate air blowing.

Calibration↗

[Two cases of multiple liver metastases (H3) from colon cancer treated by home hepatic arterial infusion chemotherapy].

Two cases with unresectable multiple liver metastases to both lobes (H3) from colon cancer, in which cases the life expectancy usually does not exceed 1 year, were treated with home hepatic arterial infusion chemotherapy employing implantable port system. They could live over one year with good performance status. Drug treatment consisted of the administration of carboplatin (CBDCA), 150 mg/body, given in a minute for one day and 5-fluorouracil (5-FU), 250 mg/body, given in a 5-hour intra-arterial infusion daily for 5 days. Cycles were administered every 2 weeks. Home hepatic arterial infusion chemotherapy using an implantable port system, which offers good local control of liver metastases, a high patient quality of life without the need for hospitalization, is suitable for treatment of unresectable liver metastases.

Antineoplastic Combined Chemotherapy Protocols↗

Characterization of YM022: its CCKB/gastrin receptor binding profile and antagonism to CCK-8-induced Ca2+ mobilization.

We investigated the antagonistic activity of (R)-1-[2,3-dihydro-1-(2'- methylphenacyl)-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl]-3- (3-methylphenyl) urea (YM022), a benzodiazepine derivative, at CCKB/gastrin receptors. This compound potently inhibited [125I]CCK-8 binding to rat brain CCKB/gastrin receptors with a Ki value of 0.26 nM, but it showed weak affinity for rat pancreas CCKA receptors (Ki = 270 nM). Selectivity for CCKB/gastrin receptors was 1000-fold greater than that for CCKA receptors. Changes in intracellular free Ca2+ concentration ([Ca2+]i) in response to CCK-8 were measured in a rat anterior pituitary cell line GH3 by fura-2 fluorometry. CCK-8 (1-100 nM) dose-dependently increased [Ca2+]i in these cells, whereas YM022 had no effect on baseline [Ca2+]i even at the highest concentration of 100 nM. YM022 inhibited the mobilization of [Ca2+]i elicited by 10 nM CCK-8 in a concentration-dependent manner with an IC50 value of 4 nM. In conclusion, YM022 is an extremely potent and highly selective antagonist of CCKB/gastrin receptors. This compound is therefore useful for studying the physiological and pharmacological roles of CCKB/gastrin receptors.

Animals↗

Proliferation and erythroid differentiation through the cytoplasmic domain of the erythropoietin receptor.

Interaction of erythropoietin (EPO) and its membrane receptor induces the proliferation and differentiation of erythroid progenitors. The molecular mechanism of the EPO receptor-mediated signal transduction remains unclear because the cloned EPO receptor does not contain any enzyme-related or nucleotide-binding consensus sequences in its cytoplasmic domain. We have previously shown that epidermal growth factor (EGF) induces dimerization of a chimeric receptor carrying the extracellular domain of the EGF receptor linked to the cytoplasmic domain of the EPO receptor, resulting in producing proliferation signals in interleukin-3-dependent cells. Here we show that this chimeric receptor transmits an EGF-dependent erythroid differentiation signal in the EPO-responsive erythroleukemia cell line, TSA8. EGF as well as EPO had little effect on the proliferation of TSA8 cells expressing the chimeric receptor, but both of them induced globin synthesis in these cells. Moreover, a truncated chimeric receptor carrying the membrane proximal 127 amino acids of the cytoplasmic domain of the EPO receptor linked to the extracellular domain of the EGF receptor conferred EGF-dependent proliferation on Ba/F3 cells and globin induction on TSA8 cells. These findings indicate that the membrane proximal region of the cytoplasmic domain of the EPO receptor is sufficient to produce both proliferation and differentiation signals if it is properly activated by receptor dimerization.

Amino Acid Sequence↗

Onset of paternal gene activation in early mouse embryos fertilized with transgenic mouse sperm.

We investigated the onset of paternal gene expression in the early mouse embryo. We obtained transgenic mouse embryos by fertilizing BD (C57BL/6N x DBA) F1 hybrid female oocytes in vitro, with sperm from homozygous transgenic males carrying integrated chicken beta-actin promoter-driven firefly luciferase cDNA. We then examined the RNA and protein synthesis of the luciferase gene in embryos from the 1- to 2-cell stage. RNA transcripts of the luciferase gene were first detected in the 1-cell stage embryos as early as 13 hr postinsemination, just prior to elongation. By photon-count imaging, functional luciferase was identified at the 2-cell stage 23 hr postinsemination. These findings indicate that the paternal endogenous gene is already transcribed in the late 1-cell embryos, although paternally derived protein is not synthesized until the 2-cell stage. Therefore, these results suggest that the embryonic gene is activated as early as the late 1-cell stage.

Actins↗

Evaluation of fecal pollution of river sediment by detection of urobilin.

In this study, we attempted to establish a new indicator for fecal pollution of river sediment using a sensitive detection method for urobilin. Urobilin contained in sediment was extracted with an alkaline buffer solution. The suitable buffer solution for extraction of urobilin consisted of 0.1 M Tris-HCl buffer (pH 10.0) containing 0.1 m sodium chloride. The ratio of sediment to buffer was 1:10. The distribution of urobilin in river sediment was studied by this method. The amount of urobilin in the river sediment of Tokyo (urban) and the Miura peninsula (rural) area was surveyed. Large quantities of urobilin were detected in the sediments of the urban rivers, but it was scarce in the rural rivers. Urobilin showed a higher content in sediment than in water. Urobilin in river sediment is distributed in large amounts in the lower reaches, where the water is polluted with domestic sewage and industrial waste, but is scarce in the upper streams. The amount of urobilin decreases to the lower layers.

Journal Article↗

Acute childhood leukemia in a patient with hemophilia: first report in Japan.

This study reports an unusual case of acute leukemia which was diagnosed as hemophilia A on initial admission for leukemia. A 3 year old boy was admitted to Kagoshima University Hospital with anemia. He was diagnosed as acute lymphoblastic leukemia. At the same time he was revealed to have severe hemophilia A- without any previous episodes of severe bleeding tendency or family history of this disease. The laboratory investigation showed his mother to be a carrier of hemophilia A. Although there are many cases of hemophilia which have developed malignant tumors, most of them were caused by association with human immunodeficiency virus (HIV) infection. Only five cases with coexistence of leukemia and hemophilia without HIV infection have been reported and the present case is the first one in Japan. At this stage, hemophiliacs are not necessarily regarded to be a population at risk for the development of leukemia. Furthermore, no particular subtype of leukemia was characterized among these patients in the literature.

Acute Disease↗

A case of non-tuberculous mycobacterial lymphadenitis diagnosed with new skin tests and PCR.

Non-tuberculous mycobacterial (NTM) cervical lymphadenitis has been rarely reported in Japan. We report on a case of a 15 month old child with NTM cervical lymphadenitis who was diagnosed with new skin tests containing NTM antigens and a polymerase chain reaction (PCR) method. These two diagnostic methods were highly useful in the present case, therefore we anticipate they will become available to other Japanese physicians to expedite the diagnosis of NTM lymphadenitis.

Humans↗

What are parents of obese children concerned about in their children?

We retrospectively examined the issues that concern parents of obese children to determine the most effective means of motivating them to seek treatment for obesity in their children. Children with an obesity index > or = 40%, aged six to 12 years, were screened in Kagoshima City in 1992. Parents were notified if their children needed an evaluation that included a family history and measurements of the blood pressure, total cholesterol, high density lipoprotein (HDL)-cholesterol, atherogenic index (ASI), triglycerides, aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Parents were informed of the results of the evaluation and invited to attend a lecture on the treatment of obesity in children. A total of 378 obese children were evaluated. However, the parents of only 39 children attended the lecture. Children whose parents attended had higher mean total levels of cholesterol (190 +/- 25 vs 175 +/- 28, P < 0.01) and ASI values (3.2 +/- 0.9 vs 2.7 +/- 0.9, P < 0.02) than those whose parents did not attend. There were no significant differences in other factors. Only 4.2% of parents whose children showed no abnormal values, except for obesity, attended the lecture, compared with 20.3% (P < 0.01) or 16.9% (P < 0.05) of parents whose children had abnormal levels of cholesterol or abnormal ASI. Parents may be more concerned about hypercholesterolemia or arteriosclerosis than obesity per se. We should perhaps use the total cholesterol or ASI values, not just the severity of obesity, to motivate parents to enter their children into treatment programs for obesity.

Adult↗

Pharmacokinetics of RK-28 (a new radiosensitizer) and pharmaceutical design of a suppository form using rats.

The pharmacokinetics of RK-28, a new hypoxic cell radiosensitizer, was studied in rats following its intravenous, intraportal, oral, and rectal administration. The pharmaceutical design of an RK-28 suppository form was also examined. After intravenous injection, RK-28 was rapidly removed from the plasma (biological half-life of 17 min) and its area under the curve (AUC) was proportional to the amount of RK-28 administered. The absolute bioavailability of RK-28 was 59.7% for intraportal administration and 36.9% for oral administration. Following oral administration of RK-28, it seems likely that specific acid-catalyzed decomposition of RK-28 takes place in the stomach and then the absorbed RK-28 undergoes first-pass metabolism in the liver. When "solidified RK-28 suppository," made by solidifying molten RK-28, was inserted into the rectum, hepatic first-pass metabolism could be avoided substantially. The resulting absolute bioavailability of RK-28 increased to 75%. Furthermore, "RK-28 emulsion suppository," prepared by emulsifying RK-28 with 1-hexadecanol and hydrogenated castor oil (HCO 60) at 80 degrees C, showed a plasma concentration-time curve very suitable for radiation therapy; the maximum plasma concentration was attained 30 min after rectal administration and then decreased within a short period. Administration of "RK-28 emulsion suppository," resulted in an absolute bioavailability of 76%.

Administration, Oral↗

Preparation and evaluation of suppositories for RK-28 (a new radiosensitizer) using rabbits.

The pharmacokinetics of RK-28 [1-(4-hydroxy-2-butenoxy)methyl-2-nitroimidazole], a new hypoxic cell radiosensitizer, was studied following intravenous, oral, and rectal administration to rabbits. After an oral administration of RK-28 solution, the plasma concentration of RK-28 was considerably lower than that after intravenous administration through all time periods, and the absolute bioavailability was a mere 4.2%. It was presumed that a specific acid-catalized decomposition of RK-28 progressed in the stomach, and also, the absorbed RK-28 suffered first-pass effects in the liver. In contrast, the absolute bioavailability following the rectal administration of a solidified RK-28 suppository preparation was significantly increased in comparison with that obtained by other administration routes. Also, RK-28 emulsion suppositories were prepared by emulsifying various amounts of the drug with 1-hexadecanol and hydrogenated castor oil (HCO 60) at 80 degrees C, and these were administered into the rabbit rectum. The resulting absolute bioavailability was 91% for the RK-28 emulsion suppository and 86.9% for an RK-28 emulsion suppository containing small amounts of Eudispert hv. These values were better than those in rats. The rectal administration of the RK-28 emulsion suppository containing small amounts of Eudispert hv showed a preferable plasma concentration-time pattern that reflects on radiation therapy.

Administration, Oral↗

[Serotonin (5-HT)3 receptors: antagonists and their pharmacological profiles].

The pharmacology of 5-HT and the classification of 5-HT receptors have become increasingly complex. However, recent advances have produced a new nomenclature system for 5-HT receptors. 5-HT3 receptors are neuronal receptors coupled directly to cation channels. Recently, many selective 5-HT3-receptor antagonists including tropisetron, zacopride, ondansetron, granisetron, zatosetron, nazasetron, YM060 and YM114 (KAE-393) have been developed. Many actions attributable to the 5-HT3-receptor have been described in both the peripheral and central nervous systems, and clinical trials are already showing the potential use of these 5-HT3 receptor antagonists in a number of disorders of the gastrointestinal tract and central nervous system, such as nausea and vomiting induced by cancer chemotherapy, anxiety, depression, schizophrenia and migraine. In addition, endogenous 5-HT is suggested to be one of the substances that mediate stress-induced responses in gastrointestinal function, i.e., increase in fecal pellet output and diarrhea. Moreover, YM060, YM114 (KAE-393) and granisetron have been reported to inhibit restraint stress- and 5-HT-induced increases in fecal pellet output and diarrhea in rats and mice, indicating that endogenous 5-HT may mediate stress-induced changes in bowel function through the 5-HT3 receptor. Therefore, 5-HT3-receptor antagonists are new therapeutic drugs for stress-induced gastrointestinal dysfunctions like irritable bowel syndrome (IBS).

Animals↗