Biomedical subjects

M Miyajima

Publications and source records attributed to M Miyajima.

At least 55 records · Page 3Linked to original sources

PubMed1997

Alterations in cytokeratin expression by the alveolar lining epithelial cells in lung tissues from patients with idiopathic pulmonary fibrosis.

It is generally recognized that epithelial cytokeratins (CKs) are expressed in tissue-specific patterns and reflect differentiation, functional specialization, and pathological alterations of the cells. Differential epithelial cell types can thus be distinguished from each other by their selective expression of particular sets of CKs. To determine the characteristics of metaplastic and hyperplastic changes of alveolar-lining epithelial cells in the lungs of idiopathic pulmonary fibrosis (IPF), the expression of individual CKs was studied immunohistochemically using monospecific anti-CK monoclonal antibodies (anti-CKs 7, 8, 10, 13, 14, 16, 17, 18, 19). Biopsy specimens from 17 patients with IPF and normal lung tissues (NL) from seven patients with lung cancer were studied. In the IPF specimens, several kinds of altered epithelial cells were observed, which showed characteristic changes in CK expression compared with NL, especially CKs 8, 14, and 17. Hyperplastic type II cells expressed increased CKs 7, 8, and 19, but not CK 17; flattened or stratified squamous metaplastic cells expressed increased CKs 17 and 14, co-expressed with CKs 7, 8, and 19; bronchiolar metaplastic cells expressed increased CKs 7, 8, and 19, co-expressed with CKs 14 and 17; cuboidal metaplastic cells expressed increased CKs 7, 8, 17, and 19. The quantification of individual CKs in the tissues by enzyme-linked immunosorbent assay revealed increased expression of CKs 8, 14, and 17 in IPF lung tissues compared with NL. These results were consistent with the immunohistochemical observations. The hyperplastic and bronchiolar metaplastic phenotypes were characterized by their increased expression of simple CKs without CK alteration. The squamous metaplastic phenotype showed CK alterations, with the appearance of CKs 17 and 14. Epithelial cells are thus altered not only in shape, but possibly also in differentiation and function, with potential implications for the pathogenesis of IPF.

Aged↗

PubMed1997

Dissolution mechanism of diclofenac sodium from wax matrix granules.

Dissolution behavior of diclofenac sodium (DS) from wax matrix granules (WMGs) prepared using a twin-screw compounding extruder is closely related to swelling ability and solubility of the rate-controlling agent employed. A swellable and soluble (hydroxypropyl)-cellulose (HPC-SL) generates both an expansion of pores inside WMGs and a structural change observed as cracking on the surface of WMGs. These changes are confirmed by mercury porosimetry. Release of DS was increased with an increase in the amount of HPC-SL in WMGs, but only 35% of DS was released from WMGs containing 73% (w/w) NaCl at the 24 h point of the dissolution. Further, no cracking was observed on the surface of NaCl-containing WMGs. A linear relationship between mean dissolution time (MDT) of DS for WMGs containing different types of HPC (HPC-SL, -M, and -H) and swelling abilities suggests that release of DS could be directly controlled by swelling of HPCs. In addition to this result, an application of the exponential model (Mt/M infinity = kt(n)) introduced by Ritger and Peppas (J. Controlled Release 1987, 5, 23-36) to DS release indicates that case II release plays a critical role in HPC-SL-containing WMGs and Fickian release is predominant in NaCl-containing WMGs since the values of n of WMGs containing 73% (w/w) NaCl and 40% (w/w) HPC-SL are 0.41 and 0.71, respectively. These results suggest that proper selection of rate-controlling agents based on their physicochemical properties (such as swelling ability and solubility) is important in designing WMGs with desired dissolution profiles.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1997

[Causative factors resulting in intractability of congenital hydrocephalus--analysis of psychomotor development and MRI findings of the brain in sixteen congenitally hydrocephalic patients].

Sixteen patients out of 58 children with congenital hydrocephalus were retrospectively investigated in terms of their psychomotor development and morphological findings of the brain by magnetic resonance imaging (MRI), and morphological backgrounds of the brain in patients affected by "intractable hydrocephalus" were intended to be clarified. The 16 patients were primarily diagnosed as having aqueductal stenosis or communicating hydrocephalus during the era before introduction of MRI. On the basis of the rate of head growth, sixteen patients were divided into three groups; group-1: overt neonatal hydrocephalus (5 cases) ; group-2: rapidly progressive hydrocephalus with normal head circumference at birth (5 cases); and group-3: slowly progressive hydrocephalus with its onset after the neonatal period (6 cases). Psychomotor development of the 16 cases was analyzed by using various methods including the Tanaka-Binet intelligence test and WISC-R. Four cases in group-1 and all cases in group-2 were found to have IQ or DQ below 50, while the other remaining cases were found to have IQ of 82 in group-1 (one case) and IQ ranging from 67 to 113 in group-3. MRI performed in those 9 cases with IQ below 50 revealed various morphological abnormalities of the brain. Those abnormalities were characterized by disturbance of organogenesis and/or histogenesis of the brain dating from the first 20 weeks of fetal life. It is strongly suggested that in the pathogenesis of intractable hydrocephalus developmental malformation of the brain occurring during the first 20 weeks of gestation are involved. Functional and morphological impairments of the brain possibly caused by progression of fetal hydrocephalus and delay of CSF diversion before and after birth seem important in the pathogenesis of intractable hydrocephalus.

Adolescent↗

PubMed1996

Overexpression of E2F1 in astrocytes leads to neoplastic transformation and changes in expression of retinoblastoma family members.

Overexpression of mouse E2F1 full-length but not truncated forms results in neoplastic transformation of astrocytes in vitro. This neoplastic transformation is accompanied with changes in cell morphology and expression of cell cycle regulators. Transformed astrocytes have higher expression of cdk2, pRb, and p107 than control astrocytes. However, expression of glial fibrillary acidic protein (GFAP) and p130 is reduced in transformed astrocytes.

Animals↗

PubMed1996

Choline acetyltransferase, nerve growth factor and cytokine levels are changed in congenitally hydrocephalic HTX rats.

The forebrain cholinergic system is correlated with learning ability and memory function. Here changes in choline acetyltransferase (ChAT) activities, nerve growth factor (NGF) concentrations and expression of IL-1 beta and IL-6 genes were determined in the basal forebrain, parieto-occipital cortex and hippocampus of hydrocephalic and nonhydrocephalic HTX rats. ChAT activity was remarkably decreased in the parieto-occipital cortex of hydrocephalic animals compared to the other two regions. On the other hand, the NGF concentration in the parieto-occipital cortex was markedly increased during the progression of hydrocephalus compared to the basal forebrain and hippocampus. IL-1 beta and IL-6 m-RNA were detectable only in hydrocephalic HTX rats. The disturbance of uptake and transport of NGF in the affected cerebral cortex is partly related to the psychomotor maldevelopment of congenital hydrocephalic children.

Animals↗

PubMed1996

Possible role of the submandibular gland in the development of obesity in mice.

The possible role of submandibular glands (SMG) in the development of obesity was studied in two types of genetically obese mice, ob/ob and yellow Ay: Obesity is caused by hyperplasia followed by hypertrophy in ob/ob mice and mainly by hypertrophy in Ay mice. The histological features of SMGs exhibited clear sexual dimorphism in both mice similar to lean controls. The SMGs of ob/ob mice was smaller in size and had smaller granular convoluted tubular portions than lean controls, while the SMGs of Ay mice did not differ from lean controls. Sialoadenectomy before and after development of obesity generally reduced the gain of body weights in both sexes of Ay mice but not in ob/ob mice. The content of epidermal growth factor (EGF) in the SMGs was higher in Ay mice and lower in ob/ob mice than their controls. The possible role of EGF in the SMGs in the development of obesity is discussed.

Animals↗

PubMed1995

Cyclin E is expressed in neurons and forms complexes with cdk5.

Expression of cyclin dependent kinase cdk5 and its regulator p35 has been shown in the cytoplasm of adult neurons. Here we demonstrate that another potential regulator of cdk5, cyclin E, is expressed in the nervous system and forms complexes with cdk5. Western blot analyses identifies expression of two forms of cyclin E in the mouse nervous system with the 56 kDa form mainly expressed in neurons and 51 kDa form expressed in astrocytes and oligodendrocytes.

Animals↗

PubMed1995

Cardiovascular selectivity of 1,4-dihydropyridine derivatives, efonidipine (NZ-105), nicardipine and structure related compounds in isolated guinea-pig tissues.

1. The cardiovascular selectivities of 1,4-dihydropyridine derivatives, efonidipine (NZ-105), nicardipine, 3NZ5NIC (the drug with NZ-105-type side-chain at C3 position and nicardipine-type at C5) and 3NIC5NZ (the drug with nicardipine-type side chain at C3 and NZ-105-type at C5) were studied in vitro. 2. All four compounds caused relaxation of guinea-pig aortae precontracted with a high K+. The pEC50 values were 7.5, 8.3, 8.1 and 5.6, for NZ-105, nicardipine, 3NIC5NZ and 3NZ5NIC, respectively. The relaxation produced by NZ-105 was slower in onset than those produced by the other compounds. The rate constant K(hr-1) of the relaxations were 0.59, 1.31, 1.02 and 1.24, for NZ-105, nicardipine, 3NIC5NZ and 3NZ5NIC, respectively. 3. In the electrically paced guinea-pig papillary muscles, NZ-105, 3NIC5NZ and 3NZ5NIC, even at concentrations as high as 10(-6) M, slightly decreased the contractile force (by 44.9 +/- 7.1%, 58.6 +/- 5.4% and 52.2 +/- 3.9%, respectively), whereas 10(-6) M nicardipine decreased the force by 84.9 +/- 3.3%. The negative inotropic effect of NZ-105 and 3NIC5NZ, but not that of 3NZ5NIC or nicardipine, was over 10 times weaker than their vasorelaxant effect. 4. In the guinea-pig right atria, NZ-105 and nicardipine at 10(-8) M decreased the spontaneous contraction rate by 67.9 +/- 15.0% and 39.7 +/- 15.4%, respectively. 3NIC5NZ at 3 x 10(-9) M and 3NZ5NIC at 3 x 10(-8) M had little effect on the rate, whereas 10(-8) M 3NIC5NZ and 10(-7) M 3NZ5NIC arrested the beating within 3 hr after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Summer-type hypersensitivity pneumonitis.

Summer-type hypersensitivity pneumonitis (SHP), the most prevalent type of HP in Japan, is caused by seasonal mold contamination in the home environment. The causative agent of the disease is Trichosporon cutaneum. The fungus grows in warm, moldy, decaying organic matter, and scatters in the air from the colonizing places. The inhaled fungi sensitize susceptible patients intratracheally and induce the disease. Glucuronoxylomannan of the fungus has a potent antigenicity that causes granulomatous alveolitis. Assay of anti-T. cutaneum antibody is very useful to establish the diagnosis of the disease because the antibody activity is virtually positive in all cases of the disease. Elimination of T. cutaneum from the colonizing places prevents recrudescence. SHP, a new form of HP, had been considered to be peculiar to Japan, but the first case of SHP outside Japan was identified in Korea last year. Soon it will be recognized in many countries of temperate and tropical clime.

Alveolitis, Extrinsic Allergic↗

PubMed1994

A new attempt to solve the scale-up problem for granulation using response surface methodology.

Scale-up from lab to production is always problematic for the development of pharmaceuticals. In granulation, an optimal formulation of binder solution determined in a lab scale is often different than that in a production scale. A new mathematical procedure to solve this scale-up problem is assessed. Granules were prepared in the two manufacturing scales (2- and 5-kg scale) by using a high-speed mixer granulator. In the manufacturing process, the binder solution plays an essential role in the formation of granules with desired physical properties, in close conformity with the manufacturing scale. A computerized optimizing technique based on a response surface methodology was developed to study the scale-up problem in the manufacturing of granules. For this purpose, a new mathematical function was introduced for the first time, which is namely an integrated optimization function. A universal optimal formulation unaffected by manufacturing scale could be obtained by minimizing the integrated optimization function. Predicted values such as yield, mean granule size, and uniformity of granule size agreed well with experimental ones on both scales. Furthermore, the optimized characteristics measured at the production scale coincided well with those obtained at laboratory scale, suggesting that this approach could be very useful in minimizing scale-up problems.

Drug Compounding↗

PubMed1994

Pyridonecarboxylic acids as antibacterial agents. VII. Synthesis and structure-activity relationship of amino- and hydroxyl-substituted 7-cycloalkyl and 7-vinyl derivatives of 1-cyclopropyl-6-fluoro-4-quinolone-3- carboxylic acid.

Novel C(7)-derivatives of 1-cyclopropyl-6-fluoro-4-quinolone carboxylic acid (3a-o) have been synthesized and evaluated for in vitro antibacterial activity. Compounds 3e (3-aminocyclobutyl), 3g (1-aminocyclopropyl), 3m ((2-aminomethyl)vinyl), and 3o ((1-aminomethyl)vinyl) showed significant inhibitory activity, comparable to that of ciprofloxacin, against gram-negative bacteria including P. aeruginosa. A good pharmacokinetic profile (serum and brain concentrations and urinary recovery) was obtained for the two cyclic compounds (3e and 3g), but that of the vinylic compounds (3m and 3o) was less favorable. Compound 3g was less toxic than 3e, ciprofloxacin, or ofloxacin in terms of acute toxicity and convulsion-induction.

4-Quinolones↗

PubMed1994

Pyridonecarboxylic acids as antibacterial agents. VIII. Synthesis and structure-activity relationship of 7-(1-aminocyclopropyl)-4-oxo-1,8-naphthyridine-3-carboxylic acids and 7-(1-aminocyclopropyl)-4-oxoquinoline-3-carboxylic acids.

4-Oxo-1,8-naphthyridine- and 4-oxoquinoline-3-carboxylic acids (2a, b and 3a-1) possessing a 1-amino-cyclopropyl group at the 7-position have been synthesized and evaluated for in vitro antibacterial activities. The three quinolones (3d, h, i) exhibited potent antibacterial activities against both gram-positive and gram-negative bacteria, which are comparable to those of ciprofloxacin (CPFX) and ofloxacin (OFLX). Among the three compounds, the best pharmacological and pharmacokinetic profile was obtained with 3i, an OFLX analogue, which was considerably less toxic than three reference quinolones (1, CPFX and OFLX).

4-Quinolones↗

PubMed1993

[Interaction of camptothecin derivatives with human plasma proteins in vitro].

The interactions of camptothecin (CPT) and its derivatives (CPT-11 and SN-38) with human plasma proteins (serum albumin (HSA) and alpha 1-acid glycoprotein (alpha 1-AGP)) were studied mainly by means of ultraviolet and fluorescence spectroscopy. The binding constants of lactone ring-opened forms (A form) of CPT and CPT-11 with HSA were larger than those of the intact lactone forms (L form). In the case of SN-38, there was no difference in the constants between A form and L form. The binding constant of CPT (A form) with HSA was larger than those of CPT-11 and SN-38. The presence of cisplatin, which is presumed to be coadministered with CPT derivatives, did not affect the interaction of CPT derivatives with HSA. Only L form of CPT-11 among the CPT derivatives examined interacted with alpha 1-AGP, followed by quenching the fluorescence of alpha 1-AGP.

Binding Sites↗

PubMed1993

[Cefuzonam penetration into cerebrospinal fluid].

We studied the penetration of cefuzonam (CZON) into the cerebrospinal fluid (CSF) in 20 patients with neurosurgical diseases. Influences of the presence of meningeal reaction and the intensity of brain damage on CSF penetration of CZON were also examined. Concentrations of CZON in serum and CSF were determined using the thin-layer cup method before and 1, 2, 4, and 6 hours after 2 g of CZON was administered intravenously. The serum concentration at 1 hour was 60.4 +/- 31.3 (mean +/- S.D.) microgram/ml, then rapidly decreased to 2.1 +/- 2.3 micrograms/ml at 6 hours. In contrast, the CSF concentration gradually increased, reached a peak level of 0.319 +/- 0.313 micrograms/ml at 4 hours and then slowly decreased to 0.273 +/- 0.249 micrograms/ml at 6 hours. The CSF penetration ration: CZON ([CSF]/[serum]) was 5.6% at 4 hours. The peak CSF concentration in patients with meningeal reaction (0.465 +/- 0.364 micrograms/ml at 2 hours) was about 2-fold higher than that in those without the reaction (0.249 +/- 0.223 micrograms/ml at 4 hours). The peak CSF concentrations in patients with slight, moderate, and severe brain damage were 0.231 +/- 0.133 micrograms/ml at 4 hours, 0.270 +/- 0.232 micrograms/ml at 4 hours, and 0.680 +/- 0.467 micrograms/ml at 2 hours, respectively. CSF penetration of CZON was augmented in patients with meningeal reaction or severe brain damage. These findings indicate that the concentration of CZON in CSF after intravenous administration is sufficient for treatment of meningitis or infections after neurosurgical operations caused by such bacteria as Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, and Streptococcus pneumoniae.

Adult↗

PubMed1992

Distribution of gonadotrophins within the anterior pituitary cells of the musk shrew (Suncus murinus L.).

Gonadotrophs in the anterior pituitary gland of the musk shrew were first identified by means of electron microscopic immunocytochemistry. The gonadotrophs of the musk shrew revealed quite unusual ultrastructural features that have never been seen before in other species. These cells contained two types of secretory granules, i.e., small dense, round-shape granules and large lucent, irregular-shape granules. FSH beta and LH beta were mostly observed together on both small and large secretory granules. The distribution pattern of the subunits of gonadotrophs was slightly altered following gonadectomy in the musk shrew.

Animals↗

PubMed1991

Potassium channel opening properties of a novel compound, NIP-121, cromakalim and nicorandil in rat aorta and portal vein.

A novel compound, NIP-121, cromakalim and nicorandil caused concentration-dependent relaxation of rat aortas precontracted with 30 mM KCl, with pEC50 (M) values of 8.2, 7.1 and 5.5, respectively. At 60 mM KCl, the vasorelaxation induced by NIP-121 or cromakalim was almost abolished whereas that induced by nicorandil remained. In preparations precontracted with prostaglandin F2 alpha(PGF2 alpha) (10(-5) M), glibenclamide (10(-7) M) and phentolamine (3 x 10(-6), 3 x 10(-5) M) antagonized the relaxation induced by NIP-121 and cromakalim but not that induced by nicorandil. Methylene blue (10(-5) M) showed antagonistic effects against the vasorelaxation induced by nicorandil but not that induced by NIP-121. NIP-121 (10(-7), 10(-6) M) and cromakalim (10(-6), 10(-5) M) significantly increased the 86Rb+ efflux rate in rat aorta. The three compounds inhibited the frequency of spontaneous contractions of the rat portal vein (pIC30; NIP-121 = 8.0, cromakalim = 7.1 and nicorandil = 4.9); glibenclamide and phentolamine antagonized the effects of these compounds. In conclusion, NIP-121 is a more potent K+ channel opener than cromakalim in these tissues. Nicorandil apparently behaves as a K+ channel opener in the rat portal vein, but the vasorelaxation may involve some other mechanisms, such as generation of cyclic GMP.

Animals↗

PubMed1991

Design of 9-beta-D-arabinofuranosyladenine (ara-A) transdermal delivery system for animal studies: regulation of drug concentration in vivo.

Transdermal delivery systems of 9-beta-D-arabinofuranosyladenine (ara-A), having controlling membranes of various permeabilities, were developed and applied to Azone-pretreated hairless mouse abdominal skin. It was confirmed that the blood concentrations of ara-A and its metabolite 9-beta-D-arabinofuranosylhypoxanthine (ara-H) in hairless mice are controlled by the permeability of the controlling membrane in the transdermal patch. Furthermore, these blood concentrations were found to closely agree with the values obtained from theoretical model calculations. Finally, but importantly, the "micropharmacokinetic" behavior of ara-A in cutaneous tissue could also be predicted. These results suggest that the transdermal patch may be employed in dermal and transdermal ara-A efficacy studies in the treatment of cutaneous herpes virus infections in hairless mice.

Administration, Cutaneous↗

PubMed1991

Esterase-like activity of human serum albumin. VII. Reaction with p-nitrophenyl 4-guanidino-benzoate.

The reaction of p-nitrophenyl 4-guanidinobenzoate (NPGB) with human serum albumin (HSA) was examined kinetically at various pH's and 25 degrees C. The Michaelis constant (Ks in M) and the catalytic rate constant (k2 in s-1) were determined. The ratio of k2 to k0 (hydrolysis rate constant of NPGB in s-1) at pH 7.4 was 75.6, indicating the esterase-like activity of HSA. The effects of the reversible binding of site-specific drugs and the chemical modification by site-specific reagents on the HSA activity indicated that HSA has multiple reactive sites towards NPGB. Results of the reaction in the presence of excess NPGB over HSA also suggested the existence of multiple active sites. The pH-profile for k2 showed inflection points at about pH 6.0 and pH 10.0, suggesting the involvement of groups with pKa's of 6.0 and 10.0 in HSA.

Benzoates↗