Biomedical subjects

A Morikawa

Publications and source records attributed to A Morikawa.

At least 181 records · Page 10Linked to original sources

PubMed1994

Natural history of B-cell dysfunction in spontaneously diabetic Chinese hamsters.

To elucidate the pathogenesis of diabetes in spontaneously diabetic Chinese hamsters (CHAD strain), a longitudinal study from just after weaning to overt diabetic state was performed. Fasting and non-fasting plasma glucose, non-fasting plasma insulin and pancreatic hormone contents (insulin, glucagon and amylin) were measured, and light microscopic examination of pancreatic islets by immunohistochemical technique and pancreas perfusion study were performed. No insulitis was found in the islets of the CHAD strain. In animals aged 1 month, there was no significant difference in the percentage of B-cell area to islet area between the CHAD strain and the control. At this stage, hyperinsulinemia was observed despite normal plasma glucose levels both in fasting and non-fasting states. In the animals of the CHAD strain aged 2-4 months, insulin secretion from the pancreas, pancreatic insulin content and non-fasting plasma insulin level decreased in proportion to the decrease of B-cell mass. In animals aged about ten months, severe hyperglycemia and hypoinsulinemia were observed. We demonstrated the existence of amylin-like immunoreactivity in the B-cells of Chinese hamsters. However, no amyloid deposit was observed in the islets of the CHAD strain. After the onset of diabetes, amylin secretion from the pancreas and pancreatic amylin content in the CHAD strain were significantly lower than those in the control. We demonstrated the natural history of B-cell dysfunction in the CHAD strain. It could mean the process of B-cell exhaustion. The profile of the CHAD strain is similar to some types of human NIDDM. Therefore, the CHAD strain is a useful diabetic model in the study of NIDDM.

Amyloid↗

PubMed1994

Localization of apoptosis (programmed cell death) in mice by administration of lipopolysaccharide.

Localization of apoptotic cells by administration of lipopolysaccharide into mice was studied by using the in situ specific labeling of fragmented DNA. This method clearly stained the nuclei of thymocytes at the cortex of the thymus. The nuclei of cells in the bone marrow and in the spleen were also positively stained. It was suggested that the cortex in the thymus is where the LPS-induced programmed cell death occurs.

Animals↗

PubMed1994

Cough variant asthma: a case study with antigen, histamine and methacholine inhalation challenge tests.

This paper presents a 7 year old girl with cough variant asthma, in which house dust challenge test provoked fine crackles on auscultation without any changes of lung function test. Pretreatment with DL-chlorpheniramine maleate for 7 days inhibited the appearance of fine crackles. On histamine inhalation test, fine crackles and rhonchi appeared on auscultation without bronchoconstriction (% fall of one-second forced expiratory volume < 10%). These data suggest that the cause of cough variant asthma is mainly an immunoglobulin E-mediated allergic reaction in the mucus secreting system.

Asthma↗

PubMed1994

Effects of cilostazol, a cyclic nucleotide phosphodiesterase III inhibitor, on substance P-induced airflow obstruction and airway microvascular leakage in guinea pigs.

We studied the effect of cilostazol, a cyclic nucleotide phosphodiesterase (PDE) III inhibitor, on a substance P (SP)-induced increase in lung resistance and in airway microvascular leakage in guinea pigs in vivo. Four minutes after intravenous (i.v.) administration of cilostazol (1.5 and 5 mg/kg) or vehicle, Evans blue dye (20 mg/kg) was given i.v. One minute later, 30 nmol/kg SP was administered i.v. The SP-induced increase in lung resistance was measured for 6 min. Following the measurement of lung resistance, microvascular leakage at the trachea, main bronchi and intrapulmonary airways was also examined. Cilostazol attenuated the SP-induced increase in lung resistance, with a significant inhibition at the concentration of 5 mg/kg. Five milligrams per kilogram cilostazol also significantly inhibited SP-induced Evans blue dye extravasation at the trachea and main bronchi. These results suggest that cilostazol might reduce airflow obstruction which is seen in diseases such as asthma through attenuation of bronchoconstriction and, possibly, airway edema resulting from airway microvascular leakage in man.

Airway Obstruction↗

PubMed1994

Theophylline attenuates circulating vitamin B6 levels in children with asthma.

This study was undertaken to investigate the effect of theophylline on circulating vitamin B6 levels in children with asthma. Twenty-six asthmatic children, including 20 patients who were treated with slow-release theophylline and 6 patients not receiving any type of theophylline preparation, were enrolled in this study. Steady state serum theophylline and vitamin B6 [pyridoxal 5'-phosphate (PLP) and pyridoxal (PL)] levels were evaluated in these patients. A depression of serum PLP levels existed in asthmatic children treated with theophylline compared to those not receiving theophylline (5.3 +/- 0.5 vs. 9.0 +/- 1.4 ng/ml, mean +/- SEM; p < 0.05). A significant negative correlation between the serum levels of PLP and theophylline was demonstrated in the subjects of this study (rs = -0.609, p < 0.001). Oral administration of 200 mg of theophylline (TheoDur) to 5 children with asthma significantly depressed serum PLP levels 4 h after the drug intake (p < 0.05), whereas theophylline did not affect serum PL levels. From these results, we conclude that theophylline induces a depression of circulating PLP levels in asthmatic children.

Adolescent↗

PubMed1994

Effect of inhaled amiloride on water-induced bronchoconstriction in asthmatic children.

To determine whether the inhaled diuretic, amiloride, can modify bronchoconstriction induced by ultrasonically nebulized distilled water (UNDW) in asthmatic children, a double-blind, randomized, placebo-controlled study was done. The UNDW inhalation challenge was performed in 12 asthmatic children (nine boys and three girls; mean age +/- SEM, 11.2 +/- 0.75 yr), who had at least a 20% fall in FEV1 after UNDW inhalation. On separate days, these subjects underwent UNDW inhalation challenge after inhalation of amiloride (0.3 mg/m2 body surface area) or placebo (0.9% saline). Neither bronchodilation nor bronchoconstriction after amiloride inhalation was observed. The mean value and SEM of the UNDW PD20 after placebo inhalation was 4.55 +/- 0.80 ml. After inhalation of amiloride, PD20 increased to 7.93 +/- 0.75 ml (p < 0.01). We concluded that inhaled amiloride exerted a protective effect against UNDW-induced bronchoconstriction in asthmatic children.

Administration, Inhalation↗

PubMed1994

Syntheses of novel galactosyl ligands for liposomes and their accumulation in the rat liver.

The effects of liposomes, bearing galactosyl ligands on their surface, on their clearance from circulation and on tissue distribution were studied in rats. The ligands were obtained through coupling 2,3,4,6-tetraacetyl-(2-[2-(2-aminoethoxy)ethoxy]ethyl)-beta- D-galactoside p-toluenesulfonate with hydrophobic anchors, followed by deprotection. We introduced mid-chain or long, branched or non-branched alipathic chains, and cholesterol as anchors. Among various anchors tested, that with a dihexadecyl branch caused the greatest accumulation of liposomes in the liver. On the other hand, liposome bearing these ligands were aggregated by Ricinus communis agglutin. This showed that these ligands were similarly incorporated to liposomes. These results show the importance of the balance between lipophilicity and the structure of ligands.

Animals↗

PubMed1994

Roxithromycin reduces the degree of bronchial hyperresponsiveness in children with asthma.

We evaluated the effects of a new semisynthetic macrolide antibiotic, roxithromycin, on the bronchial hyperresponsiveness to histamine in children with asthma. Twelve hospitalized asthmatic children, aged 11 to 15 years (mean age, 12.9 years), were enrolled in this study. They were treated with 150 mg of roxithromycin once a day orally for 8 weeks without any side effects. The PC20 value 4 or 8 weeks after the administration of roxithromycin increased significantly over the initial values (p < 0.05, p < 0.01, respectively). No significant change was observed in serum theophylline concentrations during this study. Serum cortisol level in the morning did not change after the administration of roxithromycin for 4 weeks. These results suggest that administration of roxithromycin may act favorably in the treatment of childhood asthma.

Adolescent↗

PubMed1994

Effect of theophylline on serum uric acid levels in children with asthma.

This study was undertaken to investigate the effect of theophylline on serum uric acid levels in children with asthma. Twenty-seven asthmatic children, including 21 patients who were treated with slow-release theophylline and 6 patients not receiving any type of theophylline preparation, were enrolled in this study. Serum uric acid levels were increased in the asthmatic children treated with theophylline compared to those not receiving this agent (6.28 +/- 0.29 mg/dl, mean +/- SEM, vs. 4.82 +/- 0.52 mg/dl, p < 0.05). A significant positive correlation between the serum levels of uric acid and theophylline was demonstrated in the patients of this study (rs = 0.596, p < 0.01). All the patients in whom theophylline administration was stopped showed significant decreases in serum uric acid levels (p < 0.05). From these results, we conclude that theophylline increases serum uric acid levels in children with asthma, just as it does in adult asthmatics.

Adolescent↗

PubMed1994

Age-related changes in bronchial hyperreactivity during the adolescent period.

To evaluate the influence of bronchial hyperreactivity on the improvement of asthma seen during adolescence, age-related changes of bronchial reactivity to methacholine (BRm) in adolescence were evaluated in two studies. Study 1 included 261 asthmatic children and 89 controls, aged 6-26 years, and in Study 2, yearly BRm variations from age 11 to 16 years of 23 asthmatic children of study 1 were studied. Methacholine inhalation challenge was performed by using an oscillation method; that is, respiratory resistance (Rrs) was directly measured by an oscillation technique, and subsequent doses were then doubled, until a twofold increase in Rrs from the baseline was reached. The cumulative dose of methacholine at the inflection point of the Rrs was considered to represent the BRm. From ages 6 to 9, Dmin in the asthmatic children were low (from 2.07 units to 1.38 units), but after age 12, the value gradually increased, and finally became sustained after age 16 (from 2.27 units to 4.80 units). These same age-related changes were seen in the age-matched controls. From ages 6 to 11, Dmin in the control children were also low (from 8.07 units to 12.9 units), but after age 12, Dmin gradually increased, and finally became sustained after age 16 (from 18.5 units to 43.2 units). However, for each year, the Dmin of the asthmatic children were significantly lower than those of the controls. Further, the mean of yearly Dmin variation from age 13 was less than that of younger subjects (from 0.65 unit/year to 0.92 unit/year, from 1.16 units/year younger subjects (from 0.65 unit/year to 0.92 unit/year, from 1.16 units/year to 4.16 units/year, respectively). We, therefore, concluded that the natural age-related BRm changes and the increased stability of yearly BRm variation that occur in adolescence may play a role in the improvement of childhood asthma seen during this period.

Adolescent↗

PubMed1994

[Investigation of occlusal force on lower first molar in function].

The purpose of this investigation is to detect vertically and buccolingually the occlusal force on the lower first molar in function and to make a two-dimensional vector analysis concerning the occlusal force. The subminiature occlusal force measuring apparatus, which makes use of two-dimension load cell, is developed with the apparatus equipped in the corona on the natural root of the tooth, each occlusal force on the single tooth is detected, when three subjects clench and masticate four kinds of test-foods. Conclusions are as follows: 1. Average occlusal force exerts 3.6 kgf during light clenching and 25.7 kgf during heavy clenching. The average direction of occlusal force against the tooth axis exerts 21.2 degrees during light clenching and 19.5 degrees during heavy clenching. 2. The masticatory force intensity exerts the differences in the phases of mastication and the properties of the test-foods. The maximal masticatory force is 33.1-7.9 kgf during the initial phase and 9.6-5.1 kgf during the last phase of mastication. 3. Average direction of masticatory force against the tooth axis is 19.9 degrees during the initial phase and 27.8 degrees during the last phase of mastication. 4. The operating period of masticatory force per cycle is 0.331 second on the average during the process of mastication. The longest period is in the initial phase of mastication, and as the mastication proceed it gradually decreases.

Adult↗

PubMed1993

Bradykinin is less potent in causing airway microvascular leakage in immature than in adult guinea-pigs. Role of neutral endopeptidase.

To study the effect of maturation on bradykinin-induced airflow obstruction and airway microvascular leakage, we measured changes in both lung resistance (RL) and extravasation of Evans Blue dye in anaesthetized immature (aged 12 +/- 1 days) and adult guinea-pigs (aged 77 +/- 2 days). After measurement of RL after i.v. administration of bradykinin (2.5, 5 and 10 nmol/kg) or vehicle (0.9% NaCl), dye extravasation in the lower airways was examined in the same animal. Bradykinin did not cause a significant increase in RL in immature airways, whereas even 2.5 nmol/kg induced a significant elevation in adult airways. Bradykinin-induced extravasation of Evans Blue dye was greater in adult than in immature animals. Phosphoramidon (2.5 mg/kg), a neutral endopeptidase inhibitor, did not abolish the age-related difference in the amount of dye extravasated, suggesting that mechanisms other than changes in neutral endopeptidase activity may be responsible for the lower potency of bradykinin in inducing airway microvascular leakage in immature airways.

Aging↗

PubMed1993

Platelet-activating factor-induced enhancement of superoxide anion generation in guinea-pigs.

We studied whether platelet-activating factor (PAF) enhances superoxide anion (O2-) generation in guinea-pigs. The production of O2- was assayed by chemiluminescence, using a Cypridina luciferin analog as a highly sensitive and specific probe for O2-. I.v. administered PAF significantly enhanced phorbol myristate acetate- or N-formyl-methionyl-leucyl-phenylalanine-induced O2- generation by guinea-pig alveolar macrophages or by polymorphonuclear leukocytes in a dose-dependent manner. The priming effect of PAF on O2- generation was maximal in cells harvested 5 min after administration of PAF. These responses were completely inhibited by administration of WEB 2086, a specific PAF receptor antagonist, or ONO-3708, a specific thromboxane A2 receptor antagonist, suggesting that the effects were mediated through the PAF receptor and thromboxane A2 generation. PAF might contribute to airway inflammation by enhancing O2- formation in addition to exerting other effects such as smooth muscle contraction or microvascular leakage.

Animals↗

PubMed1993

Simple measurement of glycosaminoglycan produced by cultured fibroblasts using 4-methylumbelliferyl beta-D-xyloside.

A simple and rapid method was devised for measurement of glycosaminoglycan produced by cultured cells. 4-Methylumbelliferyl-beta-D-xyloside was added to the medium of the cultured cells. After incubation, glycosaminoglycan, which was produced from 4-methylumbelliferyl-beta-D-xyloside as a primer and secreted into the medium, was separated by proteinase digestion, trichloroacetic acid treatment and ethanol precipitation. The glycosaminoglycan, bearing a fluorescent moiety at the reducing terminal, was electrophoresed on cellulose acetate membrane, and then the fluorescent band visible on the membrane was extracted. The fluorescence of the band was measured, and from this the amount of glycosaminoglycan was estimated. Using this method, it was possible to quantify a very small amount of glycosaminoglycan with relatively high sensitivity without employing a radioisotope. This method was applied for determination of glycosaminoglycan produced by cultured fibroblasts from human uterine cervix, and also the effect of a hormone on glycosaminoglycan production. It was found that uterine cervical fibroblasts produced twice as much glycosaminoglycan as skin fibroblasts.

Carbohydrate Sequence↗

PubMed1993

Attenuation of tachykinin-induced airflow obstruction and microvascular leakage in immature airways.

1. To study the effect of maturation on substance P (SP)- and neurokinin A (NKA)-induced airflow obstruction and airway microvascular leakage (MVL), we have measured changes in both lung resistance (RL) and extravasation of Evans blue dye in anaesthetized immature (aged 14 +/- 1 days) and adult guinea-pigs (aged 80 +/- 3 days). 2. RL and its recovery after hyperinflation at 5 min were measured for 6 min after i.v. SP (0.2, 1 and 30 nmol kg-1), NKA (1 and 10 nmol kg-1) or vehicle (0.9% NaCl). After measurement of RL, MVL in trachea, main bronchi and intrapulmonary airways was also examined. 3. The order of potency in inducing airflow obstruction did not change with age (NKA > SP) but immature animals required a larger dose of SP or NKA than adults to cause a significant increase in RL. 4. The order of potency in inducing airway microvascular leakage was SP > NKA in both immature and adult animals. The amount of extravasated dye after SP was significantly less in immature airways, especially in central airways. 5. Phosphoramidon (2.5 mg kg-1), a neutral endopeptidase (NEP) inhibitor, significantly increased RL after 0.2 nmol kg-1 SP only in adult airways. Phosphoramidon enhanced the dye extravasation after 0.2 nmol kg-1 SP in both immature and adult airways with a significantly greater amount of dye in adult animals, suggesting that mechanisms other than changes in NEP activity may be responsible for this age-related difference. 6. RL after hyperinflation following SP was not correlated with the degree of extravasation of Evans blue dye in immature animals, whereas it was closely correlated in adult animals. 7. SP and NKA may be less potent in causing both bronchoconstriction and microvascular leakage in immature airways. 8. Airway oedema caused by microvascular leakage may contribute less in immature airways to airflow obstruction after SP or NKA.

Aging↗

PubMed1993

The concentration of bovine IgG in human breast milk measured using different methods.

The bovine IgG concentration in human breast milk was measured using three different methods: competition radioimmunoassay (RIA), competition enzyme-linked immunosorbent assay (ELISA) and sandwich ELISA. In 36 samples of human breast milk taken from mothers on diets including cow's milk, the concentration of bovine IgG was significantly higher when measured by either competition RIA or ELISA (mean 324.9 +/- 97.4 ng/ml and 396.7 +/- 58.7 ng/ml, respectively) than by sandwich ELISA (3.44 +/- 0.48 ng/ml). In 7 samples of human breast milk taken from mothers on cow's-milk-free diets of more than one month, the concentration of bovine IgG was still within a detectable range (112.3 +/- 41.4 ng/ml) using competition ELISA, whereas it was not detected when using sandwich ELISA, suggesting that competition ELISA might measure some unknown substances in addition to bovine IgG. Gel filtration of pooled human breast milk revealed three large fractions. The concentration of bovine IgG in every fraction was significantly higher using competition compared with sandwich ELISA, suggesting that the difference between these assays does not result from measuring different quantities of bovine IgG, or of fragments of this protein. The time course of the bovine IgG level was different between each human breast milk sample after taking cow's milk. We showed that human breast milk contains bovine IgG at a concentration of approximately 3 ng/ml when analysed using sandwich ELISA. This level is comparable to the quantity of either casein or of beta-lactoglobulin in human breast milk. Bovine IgG might be an important allergen in cow's milk allergy due to the quantity in human breast milk.

Animals↗

PubMed1993

Poliovirus antibody titres, relative affinity, and neutralising capacity in maternal milk.

Varying titres of secretory IgA antibodies to poliovirus type 1 were found previously in the milk of unvaccinated, lactating Pakistani mothers during two different years, reflecting the antigenic exposure on mucosal membranes. To study further the changes in the extent and the form of antigenic exposure reflected in the human milk, human milk samples from Pakistani, Indian, Japanese, and Swedish mothers were collected. The quality and the neutralising capacity of the antibodies was also studied. Secretory IgA, IgG, and IgM antibodies to poliovirus type 1 were determined using enzyme linked immunosorbent assay (ELISA) and relative affinity was measured in ELISA by elution with potassium thiocyanide. Microneutralisation tests were also performed. The higher secretory IgA antibody titres to poliovirus type 1 in the unvaccinated, naturally exposed Pakistani and Indian mothers' milk, compared with the Swedish and Japanese mothers, presumably reflect the epidemiological situation in these countries. Neutralising capacity and the relative antibody affinity seemed to be higher both in the Pakistani mothers and the group without natural exposure but only given inactivated poliovirus vaccine, that is the Swedish mothers, than the group meeting only live vaccine strains, that is the Japanese mothers.

Antibodies, Viral↗

PubMed1993

The effect of dilazep on urinary protein excretion in spontaneous diabetic Chinese hamster.

The effect of dilazep, an adenosine potentiator and platelet aggregation inhibitor, on experimental diabetic nephropathy was investigated in spontaneous diabetic Chinese hamster. Prediabetic animals, 8 weeks of age, were divided into two groups. In one group, 5 mg/kg dilazep was injected i.p. once a day. In the other group, saline of the same amount was injected. Age- and sex-matched animals from a nondiabetic subline were used as controls. No difference was observed in body weight, mean blood pressure, fasting plasma glucose and glycated hemoglobin level between diabetic animals with and without dilazep administration throughout the entire period of experiment. Urinary protein excretions in untreated diabetic animals increased significantly compared to those of nondiabetic controls at 8 weeks (17.5 +/- 3.5 vs 2.0 +/- 0.1 mg/day), and at 24 weeks (25.3 +/- 5.1 vs 2.7 +/- 0.1 mg/day) of experiment. In diabetic animals with dilazep treatment, urinary protein excretions (4.1 +/- 0.7 at 8 weeks and 13.1 +/- 2.9 mg/day at 24 weeks of experiment) were significantly suppressed compared to those in untreated diabetic animals. Significant thickening of glomerular basement membrane (GBM) was observed in diabetic animals both with and without dilazep administration at 24 weeks of experiment compared to that in nondiabetic controls. The number of anionic sites in GBM, stained by polyethyleneimine, was reduced in untreated diabetic animals, but was not different in dilazep treated animals compared to that in nondiabetic controls. It was concluded that dilazep administration suppressed urinary protein excretion in diabetic Chinese hamster possibly through the preservation of charge barrier of the glomerulus.

Animals↗