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Biomedical subjects

N Hirose

Publications and source records attributed to N Hirose.

At least 91 records · Page 5Linked to original sources
PubMed1988

General pharmacological studies on N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate. 2nd communication: effect on the peripheral nervous system and peripheral organs.

The pharmacological actions of N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165), a new antiarrhythmic agent, on the peripheral nervous system and peripheral organs were studied in various laboratory animals in comparison with those of disopyramide and mexiletine, and the following results were obtained. 1. Large doses (50 or 100 mg/kg p.o.) of SUN 1165 as well as mexiletine had little effects on the pilocarpine-induced hypersalivation and the pupil size in mice. At higher concentration (10(-5) g/ml), SUN 1165 had no effects on the various spasmogen acetylcholine (ACh)-, histamine- or BaCl2-induced contractions in the isolated guinea pig ileum, tracheal smooth muscle and urinary bladder. Disopyramide caused mydriasis, inhibited the pilocarpine-induced hypersalivation at antiarrhythmic doses (10-30 mg/kg p.o.), and suppressed ACh-induced contractions in the various organs. 2. SUN 1165, like disopyramide and mexiletine, decreased the contractile amplitude and diastolic tone of the isolated rabbit ileum. SUN 1165 as well as disopyramide had no effect on the intestinal propulsion even at a large dose (100 mg/kg p.o.). Mexiletine inhibited it at antiarrhythmic doses (10-30 mg/kg p.o.). SUN 1165 only at a large dose (100 mg/kg i.d. or p.o.) inhibited volume of pepsin output in the gastric juice in pylorus-ligated rats and caused a damage to the gastric mucosa. 3. SUN 1165, like disopyramide and mexiletine, slightly potentiated the norepinephrine-induced contraction of the rat vas deferens in vitro. Moreover, SUN 1165 as well as disopyramide and mexiletine slightly potentiated the serotonin-induced contraction of the rat isolated fundus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Corneal endothelial changes associated with herpetic stromal keratitis.

Wide-field specular microscopy was performed on both eyes of 33 patients with unilateral herpetic stromal keratitis. Endothelial changes were quantitated by computerized morphometric analysis of individual cells. In the 16 patients with disciform keratitis, the corneal endothelium of the affected eyes showed no difference in cell density but demonstrated significant increases of variation in cell size (polymegathism) and shape (pleomorphism) when compared to the cells in the fellow unaffected eyes. The eyes with keratouveitis (17 patients), however, had marked polymegathism and pleomorphism of the endothelium and a distinctly lower endothelial cell density (mean, 19%) than the healthy fellow eyes.

Adolescent↗
PubMed1987

Isolation and characterization of four heparin-binding cyanogen bromide peptides of human plasma apolipoprotein B.

Apolipoprotein B-100 (apoB-100) is the major protein constituent of human plasma low-density lipoproteins (LDL). On the basis of its amino acid sequence [Chen, S.-H., Yang, C.-Y., Chen, P.-F., Setzer, D., Tanimura, M., Li, W.-H., Gotto, A. M., Jr., & Chan, L. (1986) J. Biol. Chem. 261, 12918-12921], apo B-100 is one of the largest monomeric proteins known with a calculated molecular weight of 512937. Heparin binds to the LDL surface by interacting with positively charged amino acid residues of apoB-100, forming soluble complexes in the absence of divalent metals and insoluble complexes in their presence. The purpose of this study was to isolate and characterize the heparin-binding domain(s) of apoB-100. Human plasma LDL were fragmented with cyanogen bromide (CNBr). After delipidation and reduction-carboxymethylation, the CNBr peptides were fractionated by sequential chromatography on DEAE-Sephacel, Mono S, and high reactive heparin (HRH) AffiGel-10; HRH was purified by chromatography of crude bovine lung heparin on LDL AffiGel-10. Heparin-binding peptides were further purified by reverse-phase high-performance liquid chromatography. Heparin-binding activity was monitored by a dot-blot assay with 125I-HRH. The amino-terminal sequences of four CNBr heparin-binding peptides (CNBr-I-IV) were determined. CNBr-I-IV correspond to residues 2016-2151, 3109-3240, 3308-3394, and 3570-3719, respectively, of the amino acid sequence of apoB-100. Each CNBr peptide contains a domain(s) of basic amino acid residues which we suggest accounts for their heparin-binding activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1987

Physical-chemical interaction of heparin and human plasma low-density lipoproteins.

This study characterizes the physical-chemical interactions of heparin with human plasma low-density lipoproteins (LDL). A high reactive heparin (HRH) specific for the surface determinants of LDL was isolated by chromatography of commercial bovine lung heparin on LDL immobilized to AffiGel-10. HRH was derivatized with fluoresceinamine and repurified by affinity chromatography, and its interaction with LDL in solution was monitored by steady-state fluorescence polarization. Binding of LDL to fluoresceinamine-labeled HRH (FL . HRH) was saturable, reversible, and specific; HRH stoichiometrically displaced FL . HRH from the soluble complex, and acetylation of lysine residues on LDL blocked heparin binding. Titration of FL.HRH with excess LDL yielded soluble complexes with two LDL molecules per heparin chain (Mr 13,000) characterized by an apparent Kd of 1 microM. Titration of LDL with excess HRH resulted in two classes of heparin binding with two and five heparin molecules bound per LDL and apparent Kd values of 1 and 10 microM, respectively. At physiological pH and ionic strength, the soluble HRH-LDL complexes were maximally precipitated with 20-50 mM Ca2+. Insoluble complexes contained 2-10 HRH molecules per LDL with the final product stoichiometry dependent on the ratio of the reactants. The affinity of HRH for LDL in the insoluble complexes was estimated between 1 and 10 microM. Insoluble LDL-heparin complexes were readily dissociated with 1.0 M NaCl, and their formation was prevented by acetylation of the lysine residues on LDL.

Animals↗
PubMed1987

Surface epithelial cell damage induced by restraint and water-immersion stress in rats effects of 16,16-dimethyl prostaglandin E2 on stress-induced gastric lesions.

The time-course of gastric mucosal surface epithelial cell damage and macroscopically visible lesions in response to restraint and water-immersion stress (22 degrees C) in rats was examined, and the effects on it of 16,16-dimethyl prostaglandin E2 (dmPGE2) were compared with those of papaverine, timoprazole and atropine. The stress produced surface epithelial cell damage prior to visible lesion, the former increasing in severity with time and reaching a plateau 60 min later, by which time exfoliation of surface epithelial cells was observable along the mucosal folds. In contrast, macroscopically visible lesions appeared 2 hr after stress, and severity continued to increase with time. Pretreatment injections (s.c.) of dmPGE2 (3, 30 micrograms/kg), papaverine (100 mg/kg) and atropine (1 mg/kg) protected the surface cells against stress (1 hr)-induced damage, and inhibited visible lesion formation after 4 hr stress. Timoprazole (30 mg/kg, s.c.) did not protect the surface cells, but did markedly inhibit visible lesion formation. dmPGE2, papaverine and atropine, but not timoprazole, inhibited stress-induced increases in gastric contractions. dmPGE2, timoprazole and atropine, but not papaverine, inhibited acid secretion in stress-conditions. These results indicated that stress induced damage to the gastric mucosa within 1 hr due to increased gastric contractions, and the surface epithelial cell damage developed into macroscopically visible lesions in the presence of acid, and that dmPGE2 protected the surface epithelium against stress-induced damage probably by inhibiting gastric contractions.

16,16-Dimethylprostaglandin E2↗
PubMed1987

Effect of nutritional status on propylthiouracil-induced protection against acetaminophen hepatotoxicity in the rat.

The effect of pair feeding of euthyroid rats compared with propylthiouracil (PTU) treated rats on acetaminophen (APAP)-induced hepatotoxicity was studied. Also, the effect of food deprivation of both the euthyroid and PTU-induced hypothyroid rats for 24 h, as well as forced feeding of the euthyroid rats after a toxic dose of APAP, was determined. Pair feeding decreased both protein and energy intake compared with ad libitum-fed controls and resulted in decreased growth rate similar to that for the PTU treated rats. In contrast to the protective effect of PTU pretreatment, decreased protein energy intake by the euthyroid rats either tended to make them more susceptible to acetaminophen-induced hepatotoxicity or had no effect as assessed by elevation of serum transaminases (SGOT,SGPT) and by hepatic necrotic score. Pair feeding also significantly altered drug disposition with an increase in the molar ratio of urinary APAP-mercapturic acid conjugate, but not the absolute amount, suggesting possible increased cytochrome P-450 dependent drug metabolizing enzyme activity. Compared with PTU-fed, in the pair-fed the molar ratio of glucuronide conjugate decreased and sulfate conjugate increased. Hepatic reduced glutathione (GSH) concentrations before and 4 h after a toxic dose of acetaminophen administration were higher in the PTU pretreated compared with euthyroid rats. Fasting of the PTU pretreated rats for 24 h after acetaminophen administration abolished the PTU-induced protective effect. Forced feeding of the euthyroid rats after a toxic dose of acetaminophen increased rather than decreased the toxicity when compared with euthyroid ad libitum-fed rats. Data suggest that higher concentrations of hepatic glutathione in the PTU pretreated compared with euthyroid rats before and 4 h after acetaminophen administration contribute to PTU-induced protection. Forced feeding of rats when the liver is severely damaged and its function compromised is harmful rather than protective. We conclude that the nutritional state of the animal significantly influences drug toxicity and should be taken into consideration in designing drug therapy and evaluation of drug toxicity.

Acetaminophen↗
PubMed1986

Structural organization of apolipoprotein B-100 of human plasma low density lipoproteins. Comparison to B-48 of chylomicrons and very low density lipoproteins.

The present study characterizes the substructural organization of apolipoprotein B-100 (B-100) of human plasma low density lipoproteins (LDL) and its relation to B-74 and B-26 of LDL and B-48 of chylomicrons and very low density lipoproteins. LDL were digested with human kallikrein and thrombin to yield two major fragments: K1 (Mr 410,000) and K2 (Mr 145,000) and T1 (Mr 385,000) and T2 (Mr 170,000), respectively. The antigenic sequences, Mr, and amino acid compositions of K1 and K2 were identical to those of plasma B-74 and B-26; B-26 and K2 had identical NH2-terminal sequences and correspond to the NH2-terminal region of B-100. K1 was further degraded by kallikrein to give K3 (Mr 235,000) and K4 (Mr 170,000); these peptides correspond immunochemically to two newly discovered plasma LDL peptides B-44 and B-30 and are assigned as complementary fragments of B-74. The thrombin cleavage fragments, T1 and T2, did not correspond to B-74 and B-26. Neither kallikrein nor thrombin generated a fragment from B-100 corresponding to B-48 in chylomicrons. However, B-48 showed antigenic homology with B-26 and to the of B-74 adjoining B-26, indicating that its structure is represented in the NH2-terminal half of B-100. The structural studies further clarify the relatedness among the B-100, B-74, B-26, and B-48 polypeptides and should now make possible the delineation of the functional domains mediating the interactions of apolipoprotein B in the circulation and arterial wall.

Amino Acid Sequence↗
PubMed1986

Effect of trypsin treatment on the heparin- and receptor-binding properties of human plasma low-density lipoproteins.

The effect of trypsin treatment on the heparin- and receptor-binding properties of human plasma low-density lipoproteins (LDL) was examined. LDL were treated with trypsin (2% by weight) for 16 h at 37 degrees C, and the trypsinized core particles (T-LDL) were isolated by gel permeation chromatography on Sepharose CL-4B. Trypsin degraded the apolipoprotein B moiety (Mr = 550,000) of LDL into numerous peptides of Mr less than 110,000, resulting in the release of 25% +/- 5% (n = 6) of its surface-associated protein. Relative to LDL, T-LDL had an increased phospholipid/protein ratio, decreased flotation density and alpha-helical structure, and increased fluidity of the surface and core constituents. Compared to LDL, T-LDL showed a 60% decreased capacity to suppress [1-14C]acetate incorporation into cellular sterols consistent with decreased binding to the LDL receptor. In contrast, T-LDL showed an enhanced capacity to form soluble complexes with heparin in the absence and presence of 2 mM Ca2+. Between 5 and 25 mM Ca2+, both LDL and T-LDL were maximally precipitated by heparin; the stoichiometry of the insoluble complexes (uronic acid/phospholipid, w/w) was 0.054 +/- 0.004 and 0.055 +/- 0.005 (n = 18) for LDL and T-LDL, respectively. Thus, trypsin treatment significantly diminished the lipoprotein's interaction with cells but not with heparin. This finding suggests that proteolysis may decrease receptor-mediated uptake of LDL without diminishing the lipoprotein's reactivity with acellular components of the arterial wall.

Cells, Cultured↗
PubMed1986

A dot-blot assay for heparin-binding proteins.

A method for the detection and quantitation of picomole amounts of heparin-binding proteins is described. Proteins are first spotted on nitrocellulose and then incubated with 125I-heparin. Binding of heparin to the proteins is detected by radioautography and quantitated by scanning densitometry; proteins are quantitated by densitometric analysis of the amido black stained nitrocellulose. Heparin-binding was time-dependent and sensitive to the presence of metal ions, urea, and detergents (anionic, nonionic, and zwitterionic). The divalent cations Ca2+ and Mg2+ and the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate increased heparin binding whereas NaCl, urea, sodium dodecylsulfate, and La3+ decreased binding. This assay is applicable to the identification and characterization of a variety of heparin-binding proteins.

Animals↗
PubMed1986

Binding of a high reactive heparin to human apolipoprotein E: identification of two heparin-binding domains.

Ligand-blotting and dot-blotting procedures were used to investigate the binding of [125I]-heparin to apolipoprotein E, its thrombin fragments E22 (residues 1-191) and E12 (residues 192-299), and to nine apolipoprotein E synthetic fragments. E22 and E12 bound [125I] heparin indicating multiple heparin-binding domains. Synthetic peptides of apoE corresponding to residues 129-169, 139-169, and 144-169, but not 148-169, bound [125I] heparin suggesting that residues 144-147 (Leu-Arg-Lys-Arg) in E22 are important for binding. Peptide 202-243 and 211-243 but not 219-243 bound [125I] heparin suggesting that residues 211-218 (Gly-Glu-Arg-Leu-Arg-Ala-Arg-Met) comprise a portion of the E12 heparin-binding domain.

Amino Acid Sequence↗
PubMed1985

Plasma GH and somatomedin C responses to single and repeated administrations of human growth hormone releasing factor (hGRF).

Plasma growth hormone (GH) and somatomedin C responses to single and repeated administrations of synthetic human growth hormone releasing factor (hGRF-44) were studied in 29 patients with GH deficiency. hGRF-44 administered by single iv bolus (10 micrograms/kg), repeated iv boluses (50 or 100 micrograms, once a day), repeated iv infusions (2.5 micrograms/min for 90 min, once a day), and/or repeated im injections (100 micrograms, twice a day) for three to six consecutive days. Ten of 16 patients had plasma GH responses to a single iv bolus injection, i.e., their plasma GH increased above 5 ng/ml or twice the basal level. However none of them showed a plasma somatomedin C increase. To repeated iv bolus injections and repeated iv infusions of hGRF-44, 7 of 17 patients showed plasma GH responses, however in none of 7 patients did somatomedin C increase. Plasma somatomedin C did not increase after repeated im administrations of hGRF-44 for 5 days. Plasma somatomedin C increase was observed in two patients, from 0.32 to 0.54 U/ml and from 0.16 to 0.46 U/ml, in response to repeated iv boluses and repeated iv infusions, respectively. These results suggest that hGRF-44 stimulates plasma GH secretion in some patients with GH deficiency, however the increases are not enough to stimulate somatomedin generation.

Adolescent↗
PubMed1985

[Hyperthermia: microwave hyperthermia in combination with intra-arterial infusion chemotherapy of cancer of the pancreas].

Fourty eight patients with cancer of head of pancreas have been treated by the intra-arterial infusion of 5-FU and Mitomycin C alone or in combination with regional hyperthermia, employing microwave machine operating at a frequency of 2450 MHz. In patients treated with intra-arterial infusion chemotherapy alone the average survival of 4.2 month was attained, whereas the average survival of 9.0 month has been seen in 39 patients treated with infusion chemotherapy and hyperthermia. The hyperthermia treatment has improved the local therapeutic effects and the effects on the survival of the patients. Thanks to this combination therapy 27 of 39 patients (69%) survived more than 6 month, and 12 patients (31%) survived more than one year, longest survival being 7 years. This study confirms that heat administered by the microwave unit potentiated the effects of the intraarterial infusion chemotherapy.

Aged↗
PubMed1985

[Changes in Y-protein and ligandin in human liver tumor tissues].

Since the relationship between tissue ligandin and liver tumors has not been studied yet, we investigated the changes of Y protein and ligandin in human hepatoma and cholangioma by gel filtration, BSP-affinity chromatography, and SDS-gel electrophoresis. The concentration of Y protein was markedly increased in both hepatoma and cholangioma, 2.8 and 4.8 times that of control, respectively. The content of ligandin was also increased in both conditions. SDS polyacrylamide gel electrophoresis of the increased ligandin confirmed the increment of 2.3 K dalton protein, which coincided with the MW of the ligandin subunit. Although the mechanism of the ligandin increase in hepatoma tissue is not clear, one possible reason might be due to the degree of differentiation of the tumor cells. In our case, the pathological examination revealed that the tumor cell was classified as Edmondoson Type II.

Adenoma, Bile Duct↗