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Biomedical subjects

M Niwa

Publications and source records attributed to M Niwa.

At least 361 records · Page 20Linked to original sources

Facile synthesis of 8-benzoylthio-2,6-methano-3-benzazocines and 3-benzoylthiomorphinans having small-ring substituents.

Synthesis of 3-cyclopropylmethyl-, 3-cyclobutylmethyl-, and 3-methyl-8-benzoylthio-2,6-methano-3-benzazocines (1j-l) was performed by regio-selective chlorosulfonation of non-narcotic 8-deoxy derivatives (1a-c) followed by reduction and benzoylation. 3-Benzoylthiomorphinans (2h-j) were also obtained by the same method. Compounds having small-ring substituents (1k, 1l, 2i, 2j) were found to be weak but pure mu- and delta-opioid antagonists. The analgetic activity of 1k was almost equal to that of pentazocine.

Analgesics↗

[Antihypertensive effect of bopindolol on stroke-prone spontaneously hypertensive rats (SHRSP)].

The antihypertensive effect of bopindolol, a long-acting beta-adrenoceptor blocking agent, was investigated in stroke-prone spontaneously hypertensive rats (SHRSP). One group received tap water during the period of 8 to 32 weeks of age. The average dose of bopindolol administered was calculated from water intake to be approximately 1.4 mg/kg/day. The lowering effect in blood pressure of bopindolol was apparent at the age of 14 weeks, and this continued up to the end of the experiment. Bopindolol significantly reduced the heart rate. Plasma levels of urea nitrogen (BUN), triglyceride, and phospholipid of SHRSP treated with bopindolol were lower than those of the control SHRSP. One of the 8 control SHRSP died, and no rats treated with bopindolol died during the experiment. The histopathological study revealed that three of the control SHRSP had cerebral apoplexy, whereas there was no evidence of cerebral apoplexy in the treated SHRSP. Chronic treatment of bopindolol clearly alleviated myocardial fibrosis and hypertrophic changes in the left ventricular wall of the heart. Decreases in the incidence of proliferative arteritis and malignant nephrosclerosis in the kidney and necrotizing arteritis of the mesenteric arteries were observed in SHRSP treated with bopindolol. The data presented indicate that bopindolol is a powerful antihypertensive agent.

Administration, Oral↗

Atrial natriuretic peptide-induced inhibition of amiloride-sensitive 22Na+ uptake into cerebral capillaries of spontaneously hypertensive rats.

22Na+ uptake into capillaries isolated from the cerebral cortex of adult (20- to 26-week-old) sustained-hypertensive spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) was compared with findings in age-matched Wistar Kyoto rats (WKY). In the presence of 1.0 mM ouabain, 1.0 mM furosemide and 2.0 mM LiCl, 22Na+ uptake into the isolated cerebral capillaries of WKY and SHR was significantly reduced to 38% and 65% of the control values, respectively, when 0.1 microM alpha-rat atrial natriuretic peptide (rANP) was added to the uptake buffer. The rANP-induced inhibition observed in SHR was significantly less, as compared with that in the WKY. Noteworthy was the observation that the Na+ uptake into the cerebral capillaries of SHRSP was not inhibited by rANP. As this peptide is thought to regulate amiloride-sensitive Na+ transport from the blood to brain by interacting with specific receptors, the present finding may relate to the etiology of dysfunction of the blood-brain barrier, in the presence of hypertension.

Amiloride↗

Characterization of insulin-like growth factor I and epidermal growth factor receptors in meningioma.

Receptors for insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) were localized and characterized in eight samples of human meningioma (four fibrous, two meningothelial, and two angioblastic types), using quantitative autoradiographic techniques. Effects of both growth factors on deoxyribonucleic acid (DNA) synthesis in the cultured meningioma cells were examined. High numbers of specific binding sites for both IGF-I and EGF were homogeneously present in tissue sections derived from fibrous and meningothelial types of meningiomas, whereas binding sites for these growth factors were not detectable in adjacent leptomeninges. While relatively large numbers of IGF-I binding sites were located in the wall of the intratumoral vasculature, the number of binding sites in the stromal component was lower in angioblastic-type meningiomas, including a low number of EGF binding sites detected only in the stromal portion. Scatchard analysis revealed the presence of a single class of high-affinity binding sites for both IGF-I and EGF in the meningiomas examined (dissociation constant (Kd) = 0.6 to 2.9 nM, and the maximum number of binding sites (Bmax) = 16 to 80 fmol/mg for IGF-I; and Kd = 0.6 to 4.0 nM, Bmax = 3 to 39 fmol/mg for EGF). Both growth factors increased the synthesis of DNA, in a dose-dependent manner, as measured by 3H-thymidine incorporation. The combination of IGF-I and EGF synergistically stimulated the synthesis of DNA, and the effects seen with 10% fetal bovine serum could be reproduced at a concentration of 10(-10) M. These observations can be interpreted to mean that both IGF-I and EGF may be involved in the growth modulation of meningiomas, possibly through paracrine or autocrine mechanisms.

Adult↗

[Dental caries of primary teeth and life habits in Shinshinotsu Nursery School: three years of observations].

It is well known that there is a high positive correlation between increases in caries increment and life habits such as use of nursing bottle, tooth brushing, between-meal eating, and sweet consumption. The purpose of this study was to analyze data of caries status in primary dentition and life habits observed in 373 Shinshinotsu nursery schoolchildren aged 3-5 years over three years. Dental examinations were conducted in good natural light using dental mirror and probe. Caries was diagnosed according to the Welfare Ministry criteria and life habits were examined by a questionnaire. The mean number of df was 7.1 for the whole sample for three years and 17.6 of the children were caries free, whereas 47.3 were more than 10 df. The former group showed the best score for the frequency of between-meal eating, frequency of sweet consumption, tooth brushing habits, and frequency of fluoride application. The latter group showed a tendency to lower sweet consumption during the three years. Our data also showed that the life habits at nursing (use of nursing bottle and weaning period) influenced incidence of caries.

Child, Preschool↗

Clinical study on the control of dental plaque using a photo energy conversion toothbrush equipped with a TiO2 semiconductor.

Adult female subjects used a toothbrush equipped with a cylindrical TiO2 semiconductor for 3 weeks. The subjects were divided into two groups, one which used the semiconductor toothbrush and the other which used a conventional toothbrush. The pl-I of the experimental group was the same as that for the control group, but showed a tendency to decrease week by week during the experimental period. The PMA-I of the experimental group during the experimental period showed a tendency to decrease, with a significant difference being observed compared to the control group after the third week. CPITN in the experimental group showed no obvious tendency towards an improvement when compared with the PMA-I value. It is suggested that improvements in gingivitis and oral cleanliness can be expected through application of the present toothbrush which is equipped with a TiO2 semiconductor.

Adult↗

Effects of beta-D-xylosides on proliferation and matrix formation of adherent fibroblastic cells in mouse bone marrow culture.

Mouse bone marrow cells were seeded on small pieces of cover glasses placed in culture dishes, and after 3 days, the pieces of glass to which only small spindle cells adhered were transferred to another dish containing fresh medium. The adherent small spindle cells proliferated and some of them became large polygonal cells with abundant cytoplasm. When phenyl beta-D-thioxyloside (0.5 mM), an artificial initiator of chondroitin sulfate chain synthesis, was added to the culture medium, the cells showed a marked increase in number as compared to controls, with conversion of about 35% of the cells to large size cells. Immunohistochemical staining with monoclonal antibodies showed that the intercellular matrix of adherent cells consists mainly of a large proteglylcan with chondroitin 6-sulfate side chains. By histochemical analysis, the amount of chondroitin sulfate was shown to be greater in the intercellular matrices of xyloside-treated groups than those of control cultures. The amount of chondroitin sulfate in the growth medium of the adherent cells, as measured by uronic acid analysis, was also significantly increased by treatment with phenyl beta-D-thioxyloside compared with controls.

Animals↗

[Dental caries of deciduous teeth in nursery school children in Shinshinotsu: changes in prevalence data for three years from 1986 to 1988].

The purpose of this study was to survey the changes in dental caries prevalence in 3-, 4-, and 5-year-old nursery school children in Shinshinotsu for 3 years from 1986 to 1988. The results obtained were as follows: 1) The caries prevalence in 5-year-old Shinshinotsu children decreased from 1986, and was 87.5% in 1988, lower than the national survey in 1987. On the other hand, the number of df teeth per person and the incidence of type C caries increased in 5-year-old Shinshinotsu children. 2) The caries prevalence rate in 3-year-old Shinshinotsu children was 89.5% in 1988, rather higher than the national survey in 1987.

Child, Preschool↗

[Expression of insulin-like growth factor I receptors in human brain tumors: comparison with epidermal growth factor receptor by using quantitative autoradiography].

By using quantitative autoradiographic techniques, receptors for insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) were analyzed in 13 samples of human brain tumors (4 low grade astrocytomas, 7 glioblastomas, 1 anaplastic ependymoma and 1 medulloblastoma). High number of specific binding sites for IGF-I and EGF were homogeneously present in tissue sections derived from glioblastoma. In low grade astrocytoma, relatively high numbers of binding site for EGF were observed, but there was no significant difference in concentrations of IGF-I binding sites between tumors and control cortex. In medulloblastoma, only IGF-I binding sites were present. These observations might indicate that both IGF-I and EGF are involved in the growth modulation of human gliomas possibly through paracrine or autocrine mechanisms. Antagonists to growth factors or monoclonal antibody against those receptors could have the way for therapeutic application for gliomas.

Astrocytoma↗

[Kappa-type opioid receptor in human placental membrane].

Since many opioid receptor preparations are heterogeneous systems containing multiple types of receptor, characterization of each type of the receptor is influenced by contamination with other types of receptor. Demonstrating kappa receptor proved more difficult owing to the ability of kappa ligands to interact with a number of receptor classes and to the lack of the homogeneous preparation. It has been reported that kappa ligands selectively bind to human placental membrane. To establish homogeneous kappa receptor preparation, the kappa binding to human placenta was characterized. The portion which was predominantly villus tissue was removed from freshly collected placenta, and the P3-membrane fraction was prepared. Kappa opioid agonist, such as 3H-Dynorphin A, 3H-ethylketocyclazocine and 3H-U-69593, bound to the human placental membrane fraction in a manner of single class of binding site (Bmax: approximately 40 fmol.mg-1 protein). In contrast, 3H-dihydromorphine, 3H-DAGO (mu agonist), 3H-DADLE (delta agonist) or 3H-SKF-10047 (sigma agonist) showed no binding activity. The specific binding of 3H-diprenorphine was displaced only by kappa-selective ligand (U-50488H, dynorphin, butorphanol). These results suggest that opioid binding in human placental membrane is specific for kappa opioid.

Humans↗

[Expression of insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) receptors in primary non-glial human brain tumors].

The expression of IGF-I and EGF receptors in the primary non-glial brain tumors (8 meningiomas, 2 neurinomas, 1 hemangioblastoma, 2 primary malignant lymphomas) was analyzed by using in vitro quantitative autoradiographic techniques. Specific binding sites for IGF-I were co-localized with those for EGF in the meningiomas and the hemangioblastoma examined. However, in the neurinomas and the malignant lymphomas, only IGF-I binding sites were present. In addition, IGF-I and EGF synergistically increased 3H-thymidine incorporation into DNA synthesis by the primary cultured meningioma cells, in dose-dependent manner. These observations can be interpreted to mean that both IGF-I and EGF may exist as autocrine or paracrine peptides involved in the growth not only of glioma but also of non-glial brain tumors.

Adult↗

Flow cytometric determination with bromodeoxyuridine/DNA assay of sensitivity of S-phase cells to cytosine arabinoside in childhood acute lymphoblastic leukemia.

The percentages of S-phase cells in leukemic and normal bone marrow cells and their sensitivity to cytosine arabinoside (Ara-C) were determined by in-vitro bromodeoxyuridine (BrdUrd)/DNA analysis in children with acute lymphoblastic leukemia. The lymphoblasts during relapse showed a higher proliferating activity than at the time of the diagnosis. The sensitivity of S-phase cells to Ara-C was measured by the percentages of the residual S-phase cells capable of incorporating BrdUrd after incubation with various concentration of Ara-C (1 ng-10 micrograms/ml). A constant dose response was found in the normal bone marrow cells of disease-free children who were in complete remission with a marked reduction of the S-phase population at a concentration of 100 ng/ml. In the leukemic bone marrow cells, in contrast, there was a wide variation in sensitivity to Ara-C. The sensitivity did not correlate with the proliferating activity of leukemic cells. In two patients, there was a good correlation between in-vitro sensitivity and clinical response to Ara-C.

Adolescent↗

Interpretation of pathophysiology by laboratory data (1). Graphic display of data, static pattern.

We have been performing the following studies over the past several years: 1) Conversion of the data of blood chemistry to a standard deviation index (SDI) as a common scale to offset differences due to measuring conditions. 2) Static global display of all the various SDI values at a single time-point on a radar chart for each patient (static radar chart). 3) Dynamic display of the pathophysiology of each patient by a radar chart (dynamic radar chart), and by a serial line graph using colors. 4) Automatic, quantitative and objective interpretation of the pathophysiology of each patient with our program at an adequate time-point selected on the dynamic display graphs. 5) Scrutiny of the interpreted results in comparison with the clinical course and data for other examinations. The present report includes details of 1), and 2).

Automation↗

Interpretation of pathophysiology by laboratory data (2). Graphic display of data, dynamic pattern.

In order to display the pathophysiology of a patient more efficiently and adequately than in the static radar chart presented in the first report, a dynamic radar chart and serial line graphs using colored lines were presented. A dynamic radar chart prepared as described particularly in this report, shows the whole data of a patient along with the time course of illness by the space-saving "overlapped-drawing". Moreover serial line graphs are employed for items important for the understanding of a patient's pathophysiology or for items which show obscure change due to overlapping in the dynamic radar chart. Although this line graph is space-occupying it reveals more clearly the changes of data throughout the entire course of a patient's disease. In this second report the dynamic presentation of data and its interpretation, were presented for nine cases. This was done more efficiently and adequately than in the cases described in the first report where the display and interpretation of pathophysiology of a patient was made using merely the data of a single point.

Biometry↗

Receptor autoradiographic evidence of specific brain natriuretic peptide binding sites in the porcine subfornical organ.

Specific binding sites of brain natriuretic peptide (BNP), a newly discovered peptide in the subfornical organ (SFO) of porcine brain were investigated, following incubation of related tissue sections with 125I-BNP, then using autoradiography and an image analysis coupled with computer-assisted microdensitometry. Specific 125I-BNP binding sites were found to be localized in the SFO, an area densely labeled by 125I-alpha-rat atrial natriuretic peptide and 125I-(Sar1,Ile8)-angiotensin II. Specific 125I-BNP binding to the SFO was displaced by unlabeled BNP, with a high affinity, and was calculated to be Ka = 0.385 x 10(-9) M and Bmax = 40.1 fmol/mg using a LIGAND computer program. Acquisition of these present findings enhances our knowledge of the physiology of BNP, atrial natriuretic peptides and angiotensin II system in the SFO.

Animals↗

Tachyplesin, a class of antimicrobial peptide from the hemocytes of the horseshoe crab (Tachypleus tridentatus). Isolation and chemical structure.

A cationic peptide, designated tachyplesin, was isolated from acid extracts of horseshoe crab (Tachypleus tridentatus) hemocyte debris. It consists of 17 residues and the structure determined by Edman degradation is: (formula; see text) The carboxyl-terminal end of this peptide was identified as arginine alpha-amide, and the whole sequence including the alpha-amide was also confirmed by fast atom bombardment mass spectrometry, indicating a mass value of 2263. Tachyplesin inhibits growth of both Gram-negative and -positive bacteria at low concentrations and formed a complex with bacterial lipopolysaccharide. Tachyplesin seems likely to act as antimicrobial peptide for self-defense in the horseshoe crab against invading microorganisms.

Amino Acid Sequence↗