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Biomedical subjects

M Nakano

Publications and source records attributed to M Nakano.

At least 739 records · Page 41Linked to original sources

Effects of antiasthma drugs on superoxide anion generation from human polymorphonuclear leukocytes or hypoxanthine-xanthine oxidase system.

Airway inflammation with human polymorphonuclear leukocytes (PMNs) may play an important role in the pathophysiology of bronchial asthma. Superoxide anion (O2-) and other active oxygen species derived from PMNs cause tissue damage. To evaluate the effects of antiasthma drugs on airway inflammation or antioxidative actions due to the inhibition of O2- generation, we investigated the effects of antiallergic drugs, beta-adrenergic agonists, theophylline and corticosteroids, on the in vitro generation of O2- by human PMNs, using a chemiluminescence (CL) method dependent on a Cypridina luciferin analog (MCLA), a highly sensitive and specific CL probe for O2-. We found that azelastine, one of the antiallergic drugs, and isoproterenol inhibited FMLP-induced O2- generation in a dose-dependent fashion, whereas the other drugs exhibited no such inhibitory action except at very high concentrations. Furthermore, we found that isoproterenol inhibited O2- generation from the hypoxanthine-xanthine oxidase system (an O2(-)-generating system) in a dose-dependent fashion, unlike azelastine and the other drugs. These results suggest that azelastine and isoproterenol inhibit the process of O2- generation from PMNs, while isoproterenol also scavenges O2-. These drugs may be beneficial in the treatment of airway inflammation due to O2- generation in bronchial asthma.

Adolescent↗

Delayed-type hypersensitivity antigens detected in culture supernatants of Salmonella typhimurium.

Protein antigens eliciting delayed type hypersensitivity (DTH) were analyzed and purified from the supernatants of protein-free cultures in which Salmonella typhimurium TV148 organisms had grown. DTH activity was measured by the footpad swelling test in mice immunized with living organisms of S. typhimurium TV148 or Escherichia coli K-12. DTH activity in the culture supernatant was specific to TV148-immunized mice. This activity was destroyed by pronase. DTH activity was unable to pass through an ultrafilter with an exclusion limit of 10 kD. After condensation of the supernatant and following centrifugation (100,000 g for 1 h), the DTH activities of the sediment and the supernatant were examined, and both showed DTH activity. Further analyses of DTH antigens in the supernatant by HPLC gel filtration separated the activity into three portions. The most active portion was further fractionated by hydroxyapatite HPLC, revealing the presence of two DTH antigens, with molecular weights of 65 and less than 10 kD. These results indicate that the culture supernatant of S. typhimurium TV148 organisms contains a variety of macromolecular protein DTH-eliciting antigens, and one of the antigens is 65 kD, which is dissociated partly by organic solvents into a low molecular weight (less than 10 kD) antigen.

Animals↗

Hypercalciuria due to combined growth hormone and calcitriol therapy in uremia: effects of growth hormone on mineral homeostasis in 75% nephrectomized weanling rats.

The administration of growth hormone (GH) in conjunction with calcitriol in uremia may increase urinary calcium and decrease renal phosphate excretion, which could have an adverse effect on the kidney in chronic renal insufficiency. The effect of 40 d of ovine GH, calcitriol, and the combination of GH and calcitriol on mineral excretion was studied in rapidly growing uremic rats. Uremia was produced by 75% nephrectomy, and the animals were fed a diet containing 8% protein with equal quantities of calcium (0.6%) and phosphate (0.6%). The uremic rats treated with ovine GH were significantly longer and heavier than the uremic control rats and the uremic rats treated with calcitriol alone. However, the combination of calcitriol and GH abolished the beneficial effect of GH on growth and increased urinary calcium excretion 4-fold over uremic controls whether expressed as calcium excretion per 100 g body weight, urine calcium to creatinine ratio, or as fractional calcium excretion. Calcitriol therapy alone also significantly increased calcium excretion, but not to the extent that the combination therapy did. This increased urinary calcium excretion in the GH plus calcitriol group was not associated with an increase in calcium and sodium intake, plasma ionized calcium, or urinary sodium excretion. The calcium content of the femurs from all uremic rat groups was significantly lower than that of the sham control rats; however, there was also no further decrease in bone calcium content in the GH plus calcitriol group compared with uremic controls. This indicated that bone was not the source of this excess urinary calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pre-column fluorescence derivatization high-performance liquid chromatography of opioid peptides in rat brain and its use for enzymatic peptide characterization.

A high-performance liquid chromatographic method involving fluorescence derivatization followed by separation on a reversed-phase polymer (octadecylated polyvinylalcohol copolymer gel) column is described for the determination of opioid peptides in rat brain tissues. The peptides extracted from brain tissues were converted into fluorescent derivatives by reaction with hydroxylamine, cobalt(II) ion and borate. The derivatives were separated on an Asahipak ODP-50 column by gradient elution of acetonitrile in the mobile phase containing borate buffer (pH 9.5). The detection limits (S/N = 3) for the peptides were 0.33-1.21 pmol per 100 microliters injected. The method actually permit the determination of leucine enkephalin, methionine enkephalin, methionine enkephalin-Arg-Phe and methionine enkephalin-Arg-Gly-Leu in the tissues. The method is also applied to the characterization of the peptides in the tissues by means of enzymatic degradations with carboxypeptidase A and trypsin.

Amino Acid Sequence↗

Transport to intestinal lumen and peritoneal cavity of intravenously administered aprinidine in rats.

Transfer of aprindine from the blood into the intestinal lumen or into the peritoneal cavity was examined after intravenous administration of the drug at a dose of 5 mg/kg in rats. The amount of the drug transferred from the blood into the intestinal lumen was much greater than into the peritoneal cavity. The average amounts of aprindine transported into the intestinal lumen and the peritoneal cavity were 0.12 and 0.03% of the dose (5 mg/kg) in 120 min, respectively. Thus, a notable difference in the clearance values of the drug was obtained between the intestinal lumen (14.8 ml/h) and the peritoneal cavity (4.94 ml/h). The net water flux showed that secretion predominated in the peritoneal transport while absorption overbalanced secretion in the intestinal transport. It seems likely that a solvent drag effect by water movement did not contribute much to the transport of aprindine from the blood to the intestinal lumen or the peritoneal cavity. The differences in transport across the two membranes could be due to differences in the surface area and other geometrical factors. Differences could also be due to a difference in the pharmacologic effects of the drug which causes a decrease in tissue splanchnic perfusion.

Animals↗

Arachidonate metabolism in bovine gallbladder mucosa.

Incubation of [1-14C] arachidonicacid (AA) with homogenates of bovine gallbladder mucosa in the presence or absence of reduced glutathione (GSH) generated large amounts of products that cochromatographed with PGE2 and 6-keto-PGF1 alpha and small amounts of products comigrating with PGF2 alpha, TxB2 and PGD2. In the presence of GSH PGE2-like material was predominantly produced while in the absence of GSH 6-keto-PGF1 alpha-like material was a major product. Identification of PGE2 was performed by its chemical conversion with NaBH4 or KOH treatments and by gas chromatography-mass spectrometry. Identification of 6-keto-PGF1 alpha was confirmed by gas chromatography-mass spectrometry. Gallbladder muscle produced predominantly 6-keto-PGF1 alpha in the presence or absence of GSH. The total amount of cyclooxygenase products was approximately 2 times higher in the mucosa than in the muscle. These results indicate that bovine gallbladder mucosa contains higher levels of fatty acid cyclooxygenase, and PGE2 isomerase and PGI2 synthetase in a proportion different from that in the muscle.

Animals↗

Influence of liver damage on antipyrine metabolite formation in rats.

1. The effects of three types of liver damage induced by carbon tetrachloride (CCl4), D-galactosamine (Ga1N) and alpha-naphthylisothiocyanate (ANIT) on antipyrine (AP) metabolism was studied in rats. 2. The serum half-life (t1/2) of AP (50 mg/kg, i.p.) was increased and total body clearance (CL) decreased in all three types of liver damage; the apparent volume of distribution (Vd) was relatively unchanged. 3. Rates of formation of AP metabolites (CLm) were lower than those in the control group in all three types of liver damage. 4. Rates of urinary excretion (% dose) of AP metabolites, 3-hydroxymethylantipyrine (HMA) and 3-hydroxymethyl-3-norantipyrine (NORA) were decreased in all three types of liver damage. However, the rate for 4-hydroxyantipyrine (OHA) was lower only in the Ga1N-treated rats. 5. The percentage conjugation of HMA was higher in the ANIT-treated rats than in the control group, and percentage conjugation of NOR was lower only in the Ga1N-treated rats. 6. These results indicate that the pathways of oxidation and conjugation of AP metabolism are not affected to the same extents by different types of liver damage.

1-Naphthylisothiocyanate↗

[Implant study of glass-ceramics in rat femurs--evaluations for dental implant applications].

In order to evaluate the possibility of dental implant application of glass-ceramics (GC), an implant study using rat femurs was performed. This GC contains crystalline apatite, wollastonite and diopside in a CaO-P2O5-MgO-SiO2-CaF2 glassy matrix. The cylindrical GC were implanted in the drilled holes of the femurs and the histologic reactions to the GC and the crystallographic changes of the GC were investigated at the timed sequence for one year. The GC provoked the endosteal bone formation. The intervening fibrous tissue between the encapsulating bone and the GC was replaced by bone tissue which was outgrowing from the encapsulating bone surface. Finally, the interface between them was bonded. The surface layer of the GC was changed morphologically and crystallographically. During these bonding phenomena, the X-ray intensities of Ca, P, Si and Mg and the crystalline pattern of the apatite crystal in this reactive zone changed. These changes might be closely related to the bone-bonding between the encapsulating bone and the GC. These results indicate the excellent biocompatibility of the GC and suggest the effective clinical application of the GC as a dental implant.

Animals↗

[Cyclosporine induced nephrotoxicity and juxtaglomerular apparatus in mice].

To elucidate the relationship between Cyclosporine (Cs) induced nephrotoxicity and juxtaglomerular (JG) apparatus, we carried out biochemical and morphological experiments using mice. Adult male ICR strain mice weighing about 40 g were used. The mice were divided into 2 groups: the Cs group (Cs 50 mg/kg/day was orally given for 14 consecutive days) and the control group (olive oil for 14 days). Urine was stored for 24 hours on the day 0, 7 and 14 and urine volume and concentrations of urinary creatinine (u-Cr) and urinary potassium (u-K) were measured in each group. All the mice were sacrificed and examined on the 15th day. Concentrations of serum creatinine (s-Cr), serum potassium (s-K), plasma renin activity (PRA), plasma aldosterone (Ald) were noted in each group. The kidneys were also examined histologically with light and electron microscopes. The Cs group showed significant increases of s-K, PRA and Ald and a significant decrease of creatinine clearance compared with the control group. Histologically, the Cs group demonstrated focal vacuolar changes in the proximal tubular cells and an increase in the number of granules in the JG cells. Each granule of the Cs group was larger than that of the control group. Cs certainly stimulates the renin-angiotensin-aldosterone system and causes consequently a secondary aldosteronism.

Animals↗

Interferon therapy for acute posttransfusion non-A, non-B hepatitis: response with respect to anti-hepatitis C virus antibody status.

To assess the effect of interferon therapy on posttransfusion non-A, non-B acute hepatitis, we examined the appearance of serum hepatitis C virus antibody (anti-HCV) and abnormal serum aminotransferase levels after the onset of hepatitis in 12 patients treated with interferon and in 46 patients treated conservatively. Eleven patients were given 3 million units of human fibroblast beta-interferon three times weekly for 4 wk and 1 was given one million units of human lymphoblastoid alpha-interferon daily for 3 months. In the interferon-treated patients, the effect of therapy on hepatic histology was also assessed. Detection of anti-HCV within 6 and 12 months after the onset of hepatitis was less common in interferon-treated patients than in control patients (6/12 vs 35/46 and 5/12 vs 35/46, both p = NS). At 24 months after the onset of hepatitis, anti-HCV levels were significantly lower in interferon-treated patients (0/10, p less than 0.05), but had not changed significantly in control patients (34/46). Abnormal serum aminotransferase levels at 6, 12, and 24 months after the onset of hepatitis were significantly less common in interferon-treated patients than in controls (25% vs 78.3%, p less than 0.005; 25% vs 71.7%, p less than 0.01; and 0% vs 67.4%, p less than 0.001). The percentage of abnormal serum aminotransferase levels at 6, 12, and 24 months after onset of hepatitis was also less in interferon-treated patients than in control patients, both among anti-HCV-positive patients (50% vs 85.7%, p = NS; 50% vs 80%, p = NS; and 0% vs 77.1%, p less than 0.01) and among anti-HCV-negative patients (0% vs 54.5%, p = NS; 0% vs 45.5%, p = NS; and 0% vs 27.3%, p = NS). Immediately after interferon therapy, the histological activity index dropped from 6.0 +/- 4.2 to 4.8 +/- 2.5 in anti-HCV-positive patients (p = NS) and from 4.2 +/- 4.3 to 2.6 +/- 1.7 in anti-HCV-negative patients (p = NS). Biopsy specimens obtained from four patients 12-23 months after interferon therapy revealed normal histology in one anti-HCV-positive patient and two anti-HCV-negative patients, and marked improvement in the other anti-HCV-positive patient. These results indicate that short-term, low-dose interferon therapy may be effective for posttransfusion non-A, non-B acute hepatitis (both anti-HCV-positive and anti-HCV-negative).

Acute Disease↗

Effects of azelastine on superoxide anion generation from gamma interferon treated human monoblast cell line U937 measured by chemiluminescence method.

U937 cells are established human monoblast cell line originally isolated from a patient with diffuse histiocytic lymphoma. In the present study, superoxide anion (O2-) generation from U937 cells were measured by 2-methyl-6-[p-methoxyphenyl]-3,7- dihydroimidazo[1,2-a]pyrazin-3-one (MCLA)-dependent luminescence. Addition of 0.5 mumol/l MCLA and a stimulatory agent, such as N-formyl-methionyl-leucyl- phenylalanine (fMLP) and phorbol myristate acetate (PMA), to a suspension of the cells treated with gamma interferon (IFN gamma) caused a marked luminescence which was inhibited by 0.5 mumol/l superoxide dismutase (SOD). On the other hand, the cells which were not treated with IFN gamma caused no significant luminescence by the stimulation with either fMLP or PMA. The adherent IFN gamma-treated cells generated more O2- than the nonadherent IFN gamma-treated cells by the stimulation with fMLP. The maximal luminescence intensity from the adherent IFN gamma-treated U937 cells stimulated by fMLP was dependent upon the number of the cells. Azelastine (A-5610, CAS 58581-89-8) significantly inhibited the O2- generation from the adherent IFN gamma-treated U937 cells stimulated by fMLP or PMA in a dose-dependent manner.

Cell Adhesion↗

Effects of antiallergic drugs on superoxide anion generation from activated human alveolar macrophages measured by chemiluminescence method.

Human alveolar macrophages were recovered by bronchoalveolar lavage and superoxide anion (O2-) generation from the macrophages were measured by 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo[1,2-a]pyrazin++ +-3-one (MCLA)-dependent luminescence. Addition of 0.5 mumol/l MCLA and a stimulatory agent, such as phorbol myristate acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP), to a suspension of the cells caused a marked luminescence which was inhibited by 0.5 mumol/l superoxide dismutase (SOD). The maximal luminescence intensity was dependent upon the number of the cells. Azelastine (A-5610, CAS 58581-89-8) significantly inhibited the O2- generation from the activated macrophages in a dose-dependent manner. However, the other antiallergic drugs, such as ketotifen, disodium cromoglycate and others showed little effects on the O2- generation from the activated human alveolar macrophages.

Bronchoalveolar Lavage Fluid↗

[Significance of intermittent CDDP therapy for improving long-term prognosis in patients with advanced ovarian cancer].

In cases of advanced ovarian cancer, intermittent CDDP therapy (ICDDPT) was applied after the first operation and induction chemotherapy, and its efficacy and limit were studied. One cycle of this therapy involved consecutive 5 day CDDP treatment (25-30mg/body/day). The therapy was repeated at intervals of 3 months. In many cases, ovarian cancer was histologically rated as epithelial adenocarcinoma. The study included 18 cases in total. ICDDPT was applied to 13 cases in which no tumor mass was detected by second look operation (SLO) or which showed clinical remission after operation. Only 3 of these 13 cases showed recurrence, and all these 13 are still living. Of the 5 cases in which SLO disclosed a tumor mass or which did not show remission after the first operation, 2 died. When the survival rate after ICDDPT was compared by the Kaplan-Meier method with that of controls without CDDP therapy, the effectiveness of ICDDPT was demonstrated. The survival rate could therefore be improved by ICDDPT. The therapy particularly improved the long term prognosis of SLO negative cases and cases in clinical remission. It seems necessary to repeat this therapy for a long period to achieve satisfactory results. In SLO positive cases and cases without clinical remission, the therapy had only a limited effect.

Adenocarcinoma↗

[Relationship between senile dementia and findings of an initial health examination--a 20 year retrospective cohort study of Kamo Village (1965 to 1985)].

The correlation between incidence of senile dementia and variables determined in baseline health examinations was analyzed in a retrospective cohort study. The study cohort was assembled in 1965 and followed up to 1985. A survey of dementia was performed on those alive in 1985, and on the decreased through their families who were queried about his or her condition just before death. The survey was conducted by public health nurses and assistants. The results obtained were as follows: 1. There was a slightly higher incidence in women and incidence for both sexes demonstrated an increase with age. 2. Analysis by cause of death showed increased death by cerebrovascular diseases for both men and women, and by cardiovascular disease for women, but decreased death from cancer. 3. Correlations of senile dementia with high blood pressure and albuminuria findings at the initial examination were seen. In addition, results of fundus oculi examination in men, and electrocardiography in women were also regarded as risk factors for the occurrence of senile dementia. 4. Comparative analysis showed higher incidence among farmers rather than fishermen, and in drinkers rather than nondrinkers, while no relation was found to smoking habits.

Adult↗