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Biomedical subjects

M Uehara

Publications and source records attributed to M Uehara.

At least 127 records · Page 7Linked to original sources

Development of a ferrocene-mediated needle-type glucose sensor covered with newly designed biocompatible membrane, 2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate.

To prepare the long-life and stable glucose sensor, we developed the ferrocene-mediated needle-type glucose sensor covered with newly designed biocompatible membrane, 2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate (MPC-co-BMA) membrane. In this membrane, the hydrophilic phosphorylcholine chains were grafted on the hydrophobic polymer surface. 1. The poly(MPC-co-BMA) membrane inhibited platelet activation and protein adhesion on the surface, showing excellent biocompatibility. These results suggested that the hydrophilic phospholipids chains might have the potential for suppressing activation and adsorption of biochemical molecules. 2. The ferrocene-mediated needle-type glucose sensor covered with poly(MPC-co-BMA) membrane achieved excellent results in vitro. Subcutaneous tissue glucose concentrations were measured in a wide range from 1.7 to more than 16.7 mmol/l. The correlation between subcutaneous tissue (Y) and blood (X) glucose concentrations was Y = 1.04X + 0.12 (r = 0.98). The subcutaneous tissue glucose concentrations could be monitored precisely for 7 days without any in vivo calibrations, and for 14 days by introducing in vivo calibrations. We therefore conclude that this sensor is stable and reliable, as compared to any other glucose sensors we developed.

Adult↗

[Haloperidol].

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Antipsychotic Agents↗

Effect on insulin sensitivity of angiotensin converting enzyme inhibitors with or without a sulphydryl group: bradykinin may improve insulin resistance in dogs and humans.

The present study compared the effect on insulin sensitivity of ACE inhibitors with a sulphydryl group (captopril) or those without a sulphydryl group (delapril and enalapril) during the hyperinsulinaemic euglycaemic clamp test in both animal and clinical experiments. A possible contribution of bradykinin to the improvement of insulin sensitivity by ACE-inhibition was also studied. In healthy control and depancreatized dog experiments, administration of captopril either intravenously (3.0 mmol.kg-1) or orally (5.0 mmol.kg-1) increased insulin sensitivity indices and plasma bradykinin concentrations. In comparison, intravenous administration of an active metabolite of delapril (3.0 mmol.kg-1) and oral administration of either delapril or enalapril (5.0 mmol.kg-1) showed slight, but not significant increases in insulin sensitivity indices and plasma bradykinin concentrations. Infusion of a bradykinin antagonist (N-alpha-adamantane-acetyl-D-Arg-[Hyp3,Thi5,8,D-Phe7]-b bradykinin) (0.5 nmol.kg-1 x min-1) abolished the effect of captopril on insulin sensitivity. Furthermore, intravenous administration of bradykinin (0.1 nmol.kg-1 x min-1) increased insulin sensitivity indices. In clinical experiments, insulin sensitivity indices decreased in the following order: normotensive healthy subjects, hypertensive non-diabetic patients, normotensive NIDDM patients and hypertensive NIDDM patients. In these four groups, oral administration of captopril (2.0 mmol.kg-1) significantly increased insulin sensitivity indices, and a concomitant increase in plasma bradykinin concentrations was observed. By contrast, oral administration of enalapril or delapril showed slight, but not significant effects on insulin sensitivity indices and plasma bradykinin concentrations. From these studies, it is concluded that ACE inhibitors with a sulphydryl group have more potent action on the improvement in insulin sensitivity than those without a sulphydryl group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

Effect of herbimycin A, an inhibitor of tyrosine kinase, on protein tyrosine kinase activity and phosphotyrosyl proteins of Ph1-positive leukemia cells.

Herbimycin A, a benzoquinonoid anasamycin antibiotic, preferentially inhibited the in vitro growth of Ph1-positive leukemia cell lines. On the other hand, genistein, which was developed as an inhibitor of receptor-type tyrosine kinase, and other protein kinase inhibitors showed no selective inhibition of Ph1-positive leukemia cell growth. Herbimycin A also displayed an abrogative effect on the transformation of murine hematopoietic cells by transfection with a bcr/abl oncoprotein-expressing retroviral vector. The antitumor action of herbimycin A on Ph1-positive leukemia cells is related to an inhibition of activity of bcr/abl protein tyrosine kinase and a subsequent reduction of the constitutive phosphotyrosyl proteins, however, the antibiotic has no effect on the expression of bcr/abl mRNA and oncoprotein. Therefore, herbimycin A may provide an important insight into the oncogenic action of bcr/abl oncoprotein and the future development of oncoprotein-targeted therapeutic agents.

Antibiotics, Antineoplastic↗

Changes in causes of death in diabetic patients based on death certificates during a 30-year period in Osaka District, Japan, with special reference to cancer mortality.

As reported previously, we have conducted studies on causes of death among diabetic patients during the 25-year period, from 1960 to 1984, in Osaka District, Japan. We have now added the most recent 5-year data, for 1985-1989, and analyzed changes in causes of death during the entire 30-year period as a whole. The subjects studied were those for whom a total of 32,222 death certificates had been filed in Osaka Prefecture, from 1960 to 1989, with diabetes mentioned either as the underlying cause or as a contributory condition. The relative number of death certificates mentioning diabetes as the underlying cause, which had been decreasing during the 25-year study period, showed a further decrease, reaching the lowest value, 33.4%, for the period 1985-1989. The mean age at death exceeded 70 years for all causes of death, showing a continuous increasing trend. An increase in disease of the heart and a decrease in cerebrovascular disease were observed, making the difference between the two causes greater since 1980-1984. Malignant neoplasms, ischemic heart disease, and pneumonia and bronchitis also showed steady increases. The O/E ratios (ratio of observed/expected number of deaths) for cirrhosis of the liver and tuberculosis were markedly increased, while that for malignant neoplasms was only about 0.5, suggesting extreme underestimation of the number of diabetic cases with cancer. Among malignant neoplasms, an increasing trend in liver cancer was remarkable and was associated with a relatively high O/E ratio.

Age Factors↗

Anatomical and histological re-examination of Appendices colli in the goat.

Appendices colli (App. colli) were investigated by anatomical and histological methods in the goat. App. colli were composed of elastic cartilage located at central and the skin covering the cartilage, which included arterioles along the cartilage and nerve bundles. Three types of muscles connected to App. colli; superficial muscle bundles, a branch of the omohyoideus muscle, and a muscle arising from the pharyngeal raphe (appendico-pharyngeal muscle). The latter two muscles were connected to the root of the App. colli where the muscle fibers transformed into the perichondrium of the elastic cartilage. The appendico-pharyngeal muscle was innervated by branches from the glossopharyngeal nerve which were composed of myelinated nerve fibers. The subcutaneous area of the App. colli was supplied by cutaneous rami of the vagus and the second cervical nerves. The innervation and the musculature confirmed that the cartilage of the App. colli were derived from third and fourth branchial arches.

Animals↗

Histopathological features of recalcitrant erythema of the face in adult patients with atopic dermatitis.

Recalcitrant erythema on the face of 21 adult patients with atopic dermatitis was histologically examined. All patients had been applying topical corticosteroids to the facial erythema for three years or more. The histopathology of the recalcitrant facial erythema was not homogeneous. Thus, the facial erythema was roughly classified into three categories: 1) erythema which mainly showed eczematous changes, 2) erythema which mainly showed steroid-induced rosacea-like changes, and 3) erythema which showed both eczematous changes and steroid-induced rosacea-like changes. The majority (75%) of recalcitrant facial erythema belonged to the third category.

Adult↗

Patch test reactions to the acetone-soluble fraction of human dander in atopic dermatitis.

An acetone-soluble fraction of human dander provoked positive patch test reactions in 45 (38%) of 120 patients with atopic dermatitis. The positive patch tests were rare in normal controls and clinical controls. The positive patch test reactions histologically showed spongiosis and mononuclear cell migration in the epidermis, edema and mononuclear cell infiltrate in the upper dermis. Scratch tests with the acetone-soluble human dander fraction were positive in only 2 (2%) of the 120 patients examined. It was suggested that in a considerable number of patients with atopic dermatitis, an acetone-soluble fraction of human dander provokes a delayed-type skin reaction without inducing an immediate-type skin reaction.

Acetone↗

[Analysis of antigenic peptides obtained from Japanese birch pollen].

Allergic rhinitis caused by birch pollen is common in parts of Northern Europe, North America and the northern Japanese island of Hokkaido. The major antigenic fragment of European birch (Betula verrucosa) pollen allergen with a M. W. of 17k dalton was isolated and termed Bet vI. The amino acid sequence of Bet vI has already been identified. We have attempted to identify an antigenic peptide of Japanese birch (Betula platyphylla var. Japonica) pollen allergen. Seventeen Kd fragments separated from pollen allergen by SDS-PAGE were shown to bind with IgE in the pooled sera of pollinosis patients. The fragment was digested with trypsin and fractionated by reverse phase HPLC. Five fractions were identified to have in vitro activities, such as the lymphocyte proliferative response, in pollinosis patients. Amino acid sequences of peptides in the fractions were determined. The sequence of a 12-mer peptide was shown to correspond to that of No 22-33 of Bet vI, except for the amino acid at the 31st position, phenylalanine, which was instead isoleucine. Synthetic peptides based on this sequencing were shown to cause proliferation of lymphocytes, derived from pollinosis patients, which was blocked by monoclonal antibodies to HLA-DR molecules.

Amino Acid Sequence↗

Ultrastructure of blood vessels in the head kidney of the carp, Cyprinus carpio.

The ultrastructural features of blood vessels were examined by transmission and scanning electron microscopy in the perfused and nonperfused head kidney of the carp. They consisted mainly of the sinusoidal capillaries, arterioles, veins and portal veins. The sinusoidal capillaries were composed of endothelial cells that frequently exhibited large pores and an indistinct basal lamina. Some endothelial cells were trabecular in shape and protruded into the lumen. The reticular cells frequently attached to the outside of the endothelial cells, and macrophages were located on the luminal and abluminal surfaces of the endothelial cells. The arterioles possessed continuous endothelial cells with a thick basal lamina, continuous smooth muscle layers and a thick adventitia with collagen fibres and reticular cells. The veins were characterised by fenestrated endothelial cells and thin connective tissue. The portal veins were composed of continuous electron-lucent endothelial cells and thick layers of reticular cells and collagen fibres. The differences between the endothelial cells in each blood vessel probably reflect the various functions of the carp head kidney. The ultrastructural features of the sinusoids and the portal veins resemble those of lymphatic vessels of mammals and appear to relate to macrophage and lymphoid cell migration and proliferation in the carp head kidney.

Animals↗

[Analysis of birch pollen allergen].

Birch Pollen is one of common causal agents of nasal allergy (pollinosis) in Hokkaido, Japan. We have previously reported the positive association of the pollinosis with HLA-DR9 antigens. It was reported by others that Bet vI, a 17kDa protein with known amino acid sequences represented the major allergen of birch pollen in Europe. We have tried to determine the location of possible allergenic activity on the 17kDa protein of Japanese birch pollen (Betura Platyphylla var. Japonica). In this study, we have examined the lymphocytes proliferative response (LPR) for trypsin digested materials of a 17kDa protein obtained from Betura Platyphylla var. Japonica. The strong response of lymphocyte was observed against the peptide fragments composed of amino acids from 22nd to 33rd (22-33) and from 56th to 66th (56-66) of the Bet vI molecule. It was also found that our 17kDa protein had isoleusine substitution for phenylalanine at position 31. By using synthetic peptides, we showed that asparagine at position 29 of 22-33 and glutamic acid at position 61 of 56-66 were critical for LPR.

Allergens↗

Impaired ability of neutrophils to produce oxygen-derived free radicals in patients with chronic liver disease and hepatocellular carcinoma.

To evaluate whether neutrophil bactericidal function, the ability to produce oxygen-derived free radicals, is altered in patients with chronic liver disease, we measured chemiluminescence amplified by a luciferin analog (Cypridina luciferin analog-dependent chemiluminescence) and luminol (luminol-dependent chemiluminescence) in response to N-formyl-Met-Lue-Phe by neutrophils from patients with chronic liver diseases due to C and/or B type hepatitis: chronic active hepatitis, cirrhosis and hepatocellular carcinoma. Both Cypridina luciferin analog-dependent chemiluminescence and luminol-dependent chemiluminescence were significantly decreased in neutrophils from patients with chronic liver disease (hepatocellular carcinoma < cirrhosis < chronic active hepatitis) when they were compared with normal healthy subjects. The reduction of Cypridina luciferin analog-dependent chemiluminescence in chronic active hepatitis and cirrhosis was more sensitive than Cypridina luciferin analog-dependent chemiluminescence; however, in hepatocellular carcinoma, luminol-dependent chemiluminescence was more reduced than luminol-dependent chemiluminescence. Although there were not significant correlations between glutamic pyruvic transaminase and Cypridina luciferin analog-dependent chemiluminescence/luminol-dependent chemiluminescence, there were significant negative correlations between total bilirubin and Cypridina luciferin analog-dependent chemiluminescence/luminol-dependent chemiluminescence. Furthermore, there were significant positive correlations between albumin/prothrombin time and Cypridina luciferin analog-dependent chemiluminescence/luminol-dependent chemiluminescence. These data suggest that an impaired ability to produce oxygen-derived free radicals may contribute to the susceptibility to infection in patients with chronic liver disease.

Alanine Transaminase↗

Bioactive glass promoted formation of nodules in periodontal-ligament fibroblasts in vitro.

The effects of bioactive glass and vitamin D3 on cultured fibroblasts derived from periodontal-ligament, with respect to their proliferation and alkaline-phosphatase activity were studied. The cells were cultured with or without the bioactive glass and/or vitamin D3, then the number and alkaline-phosphatase activity of the cells were measured periodically until the 33rd day. Formation of mineralized deposits was assessed by staining with alizarin red and von Kossa staining techniques. Fewer fibroblasts grew when they were cultured in the presence of bioactive glass and/or vitamin D3 as compared to those cultures without them. Alkaline-phosphatase activity was greater in the fibroblasts cultured with bioactive glass and vitamin D3 than in the cells grown without them. Mineralized deposits assessed by alizarin red and von Kossa staining techniques were observed microscopically around the fibroblasts cultured with bioactive glass and/or vitamin D3. A nodule visible after drying was evident only when both bioactive glass and vitamin D3 were present in culture. The results showed that although the bioactive glass and vitamin D3 decreased cell proliferation, they increased the alkaline-phosphatase activity of the fibroblasts which formed a nodule, suggesting an effect which might be useful for implant materials.

Alkaline Phosphatase↗

Noninvasive measurement of blood glucose concentrations by analysing Fourier transform infra-red absorbance spectra through oral mucosa.

Whether Fourier transform infra-red spectroscopy with an attenuated total reflection prism could be applied for noninvasive glucose measurement through oral mucosa was evaluated. As a result, the same absorbance peak at 1033 cm-1 as in glucose aqueous solution was found in the absorbance spectra through mucous membrane. However, these glucose specific peaks were interfered with by the baseline drifts owing to prism attachment and the background spectra from body constituents other than glucose. Therefore, to eliminate these interferences, the calibration curve between the second derivatives of the absorbance peak at 1033 cm-1 and those at 2920 cm-1 was calculated (r = 0.910). By using this calibration curve, the spectral changes due to prism attachment were first eliminated. Secondly, by obtaining the second derivative of the difference between the postprandial absorbance peak and the fasting sample as a characteristic of an individual, high correlations between the corrected second derivatives of absorbance spectra through the mucous membrane of the lip at 1033 cm-1 and the increases in blood glucose concentrations above fasting levels were observed (r = 0.910). In conclusion, it was suggested that Fourier transform infra-red spectroscopy could be useful for noninvasive monitoring of glucose through oral mucosa.

Blood Glucose↗

The proportion of death certificates of diabetic patients that mentioned diabetes in Osaka District, Japan.

To determine the accuracy of the stated causes of death in diabetic patients, we analyzed 503 death certificates of diabetic patients who had been followed up for 9.4 years on average at Osaka Medical Center for Adulthood Diseases and had died during the observation period from 1960 to 1984. Of the certificates examined, only 213 (42.4%) mentioned diabetes, either as the underlying cause or as a contributory condition. The proportion of certificates that mentioned diabetes was related to the underlying cause of death; it was 18.7% for malignant neoplasms, 40.5% for cerebrovascular disease and 46.9% for disease of the heart, while it was 81.8% for renal disease. The proportion was higher for females (48.7%) than for males (39.5%), and a significant difference was observed between the sexes in the proportion in the case of disease of the heart. The proportion was not related to any significant extent to the year of death or the age at death. However, it was related to fasting plasma glucose (FPG) level and type of treatment. It was 37.8% and 54.4% for patients with FPG < 200 mg/dl and FPG > or = 200 mg/dl, respectively, 24.1% for those treated with diet, 51.4% for those treated with oral hypoglycemic agent and 80.7% for those treated with insulin. As a result, it was found that the proportion of death certificates that mentioned diabetes was related to the accompanying complications and the severity of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Cause of Death↗

Melanotrophs of Xenopus laevis do respond directly to neuropeptide-Y as evidenced by reductions in secretion and cytosolic calcium pulsing in isolated cells.

Neuropeptide-Y (NPY) is present, along with dopamine and gamma-aminobutyric acid, in the neurons innervating the intermediate lobe of the pituitary gland of Xenopus laevis, and all three neurotransmitters have been shown to inhibit melanotroph secretion from isolated neurointermediate lobes. However, unlike dopamine and gamma-aminobutyric acid, NPY has been reported to be without inhibitory effect on secretion from dispersions of intermediate lobe cells. Moreover, binding studies have been taken as indicating that Xenopus melanotrophs lack NPY receptors, although such receptors appear to be present on folliculostellate cells. For these reasons, NPY has been considered to act indirectly on Xenopus melanotrophs; the putative intermediary is supposed to be the folliculo-stellate cell. However, the present experiments show that NPY does strongly inhibit melanotroph secretion from cells dispersed from Xenopus intermediate lobes. In addition, they demonstrate that NPY acts directly on individual Xenopus melanotrophs (immunohistochemically identified and under conditions that preclude any interaction between cells) to inhibit the intermittent rises in cytosolic free Ca (cytosolic Ca pulsing). From these observations, we conclude that NPY does act directly on melanotrophs of Xenopus.

Animals↗

Effect of a monoclonal anti-sperm antibody (A-1) on in vitro fertilization in the mouse.

We prepared four monoclonal antibodies raised against mouse spermatozoa. The ability of the hybridoma culture supernatants to inhibit in vitro mouse fertilization was determined. One of these monoclonal antibodies, termed A-1, strongly inhibits sperm penetration into zona pellucida of egg in a concentration-dependent fashion. On the other hand, even in the presence of the same concentration of A-1 antibody, sperm binding to comulus-free eggs was slightly inhibited and sperm-egg fusion was not inhibited at all. Immuno-fluorescence studies with A-1 showed that it recognizes an antigen(s) localized in the acrosome of mouse spermatozoa. In the case of unfixed sperm, the acrosome-intact sperm (i.e., sperm bound to egg zona pellucida) and unbound sperm were slightly immunostained with A-1 antibody (1.6% and 9.0%, respectively). All the full acrosome reacted sperm (i.e., sperm penetrating into the perivitelline space) were not immunoreacted. On the other hand, when sperm were fixed with methanol, approximately 80% of unbound sperm were immunoreacted with this antibody. Furthermore, almost all of zona-binding sperm were immunostained, whereas acrosome reacted, penetrating sperm were not. These data suggested that the antigen recognized by A-1 was located inside the plasma membrane of spermatozoa, and appeared on the surface of the spermatozoa during the period of penetration into egg zona pellucida. After sperm penetration into the perivitelline space this antigen must be released from the sperm.

Animals↗