Search PubMed⌕ Search

Biomedical subjects

H Matsukura

Publications and source records attributed to H Matsukura.

At least 19 recordsLinked to original sources
PubMed1997

Clinicopathological characteristics of the focal and segmental form of idiopathic membranous nephropathy: comparison with the typical form of this disease.

Although idiopathic membranous nephropathy (IMN) is thought to represent a diffuse glomerulopathy, it was found that three of 31 children histologically diagnosed as IMN showed focal and segmental deposition of immunoglobulin G (IgG) and C3 on the glomerular capillary walls. The present study attempted to comparatively investigate clinical and pathological features of the diffuse group and the focal segmental group in 31 IMN children. Immunofluorescence study revealed that 28 of 31 IMN exhibited diffuse granular deposition of IgG along glomerular capillary walls. In contrast, focal and segmental deposition of IgG and C3 was noted in three children with IMN. In addition, focal and segmental electron-dense deposits were identified in these cases. In two children of the focal segmental group, immunofluorescent patterns of IgG deposition were unchanged even at the second biopsy. The focal segmental form of IMN tended to occur in younger children than diffuse IMN. However, other clinical parameters such as the range of proteinuria, hematuria, serum albumin and prognosis did not show any significant differences between both groups. Electrophoretic profiles of urinary proteins on sodium dodecylsulfate-polyacrylamide gel electrophoresis were not different between both groups. It is proposed that the focal segmental form of IMN may have a distinctive glomerulopathy from the typical form of IMN.

Child, Preschool↗
PubMed1997

Photodegradation products of a new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution.

A new antibacterial fluoroquinolone derivative, orbifloxacin (ORFX), is decomposed photochemically in aqueous solution. When ORFX solution was irradiated with a chemical lamp or sunlight, three major photodegradation products were isolated by preparative HPLC. These degradation products were identified by electron-impact mass spectrometry, liquid-secondary-ion mass spectrometry and 1-H-NMR spectroscopy. Moreover, the photodegradation pathway was investigated by a similar study using several fluoroquinolone derivatives which were presumed to be the intermediates of the photoreaction of the ORFX. Consequently, it was found that two main photochemical reactions, the decomposition of the dimethylpiperazinyl moiety and the elimination of the cyclopropyl group, take place in ORFX. The detected structures of photodegradation products and the photodegradation studies of the postulated intermediates suggested that the photodecomposition of the dimethylpiperazinyl ring at the 7-position and the elimination of the cyclopropyl group at the 1-position occurred concurrently with the release of fluorine at the 8-position.

Anti-Infective Agents↗
PubMed1996

Serum tumor necrosis factor in mesangial IgA glomerulonephritis with macroscopic hematuria in children.

Tumor necrosis factor (TNF)-alpha and interferon (INF)-gamma levels were measured in the sera obtained from 29 patients with IgA glomerulonephritis (IgA GN), 8 patients with minimal change nephrotic syndrome (MCNS) and 12 patients with upper respiratory tract infection (URI) without renal diseases in children. The serum TNF-alpha level of IgA GN was 123.0 +/- 175.4 pg/ml, MCNS was 4.9 +/- 4.0 pg/ml and URI was 10.5 +/- 4.5 pg/ml respectively. The serum TNF-alpha level of IgA GN was significantly higher than those of MCNS and URI. The serum TNF-alpha level of URI was on the high trend compared with that of MCNS, but was not statistically significant. Although the TNF-alpha level was related to mesangial cell proliferation in patients with IgA GN, it was unrelated to the grade of mesangial matrix expansion and magnitude of proteinuria. In 17 patients with IgA GN having macroscopic hematuria, the serum TNF-alpha level was 190.5 +/- 201.6 pg/ml, and in other IgA GN patients with microscopic hematuria it was 37.4 +/- 75.7 pg/ml. The serum TNF-alpha level of IgA GN with macroscopic hematuria was significantly higher than that with microscopic hematuria. In 6 patients with IgA GN with macroscopic hematuria, the serum TNF-alpha level was significantly decreased after macroscopic hematuria disappeared. The mean serum IFN-gamma level of IgA GN was 0.3 +/- 0.6 IU/ml, and MCNS was not detectable. Although the serum IFN-gamma level was related to mesangial cell proliferation in patients with IgA GN, it was unrelated to magnitude of proteinuria, the grade of mesangial matrix expansion and also the presence or absence of macroscopic hematuria. We suggest that macroscopic hematuria of IgA GN was closely related to the serum TNF-alpha level.

Adolescent↗
PubMed1996

Decrease of mesangial matrix after immunosuppressive therapy in children with reversible membranoproliferative glomerulonephritis type I.

We followed the course of membranoproliferative glomerulonephritis (MPGN) type I after immunosuppressive therapy in 10 children. At diagnosis all patients had abnormal urinary findings. After a mean follow-up of 14 years all but one patient showed normal urinalysis and renal function. Glomerular morphometry revealed an increase in the ratio of mesangial matrix area to glomerular area (M/G%) in all patients. After immunosuppressive treatment, a second biopsy was performed, which showed a significantly decreased M/G% in 4 patients. In 3 of the remaining 6, the mean M/G% was significantly lower in a third biopsy when compared with the first. In addition, there was a negative correlation between M/G% and duration from onset disease to biopsy (r = -0.46, p <0.05). Fifteen biopsies (6 initial and 9 repeat biopsies) were examined for the staining of various extracellular matrices. In the initial biopsy type IV collagen, type V collagen and fibronectin were increased in expanded mesangial areas. Type III collagen was found segmentally in a few biopsies only. M/G% correlated with the grade of type IV collagen, type V collagen and fibronectin staining. These findings suggest that a reversible clinical course of MPGN type I in children is paralleled by a decrease of mesangial matrix expansion.

Adolescent↗
PubMed1995

Photodegradation kinetics of the new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution.

The photodegradation kinetics of orbifloxacin (1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(cis-3,5-dimethyl-1-pipe raz inyl)-4-oxoquinoline-3-carboxylic acid) was investigated in aqueous solution at various pH values (1.2-12.5) and at an ionic strength of 0.5. The photodegradation experiments were performed using a fluorescent or a chemical lamp as a light source and the cumulative number of photons during exposure was determined by a ferrioxalate actinometer. It was found that the photodegradation of orbifloxacin followed apparent first-order kinetics under both types of artificial light. The photodegradation rates of orbifloxacin in a neutral medium were higher than those in acidic and alkaline media. Orbifloxacin was most unstable in solution at pH 7.4, and its degradation half-life was 0.9 h. Also, the log k-pH profile indicated that the photodegradation rate of orbifloxacin was related to the dissociation of the carboxylic and dimethylpiperazinyl groups and the main photo-labile species was the zwitterionic form. In addition, the photodegradation kinetics of the decarboxylated derivative of orbifloxacin in aqueous solution was investigated to determine the effect of the functional groups on the photodegradation of orbifloxacin.

Anti-Infective Agents↗
PubMed1995

Degradation kinetics of the new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution.

The degradation kinetics of orbifloxacin [1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(cis-3,5-dimethyl-1-pipe raz inyl)-4-oxoquinoline-3-carboxylic acid] was investigated as a function of pH (1.5-10.5), temperature (100-120 degrees C) and buffer concentration (0.05-0.2 M) by means of high-performance liquid chromatography. The degradation of orbifloxacin in aqueous solution followed apparent first-order kinetics under all experimental conditions. No appreciable effect of buffer on the degradation of orbifloxacin was observed for any of the buffer species used in this study. The log k-pH profiles indicated specific-acid and specific-base catalyses and there were inflection points near pH 6 and 9 corresponding to the pKa1 and pKa2 values. From the Arrhenius plots, the activation energies for k'H, k'H2O, kH2O, k"H2O and k"OH were found to be 31.9, 36.9, 23.5, 26.5 and 19.0 kcal/mol, respectively. Arrhenius data obtained from this study showed that the degradation of orbifloxacin at room temperature was negligible at all pH values studied conditions (pH 1.5-10.5).

Anti-Infective Agents↗
PubMed1994

[Studies on the inhibitory action of leminoprazole against rabbit gastric H+,K(+)-ATPase].

Inhibitory action of leminoprazole ((+/-)-2-[[2-(isobutylmethylamino)benzyl]sulfinyl]-1H-benzimidazol e, NC-1300-O-3, LEM) against the H+,K(+)-ATPase activity in rabbit gastric vesicles was investigated. LEM inhibited the H+,K(+)-ATPase activity in leaky vesicles in a concentration- and time-dependent manner. When preincubated with gastric vesicles (20 micrograms protein/ml) for 30 min at 37 degrees C in medium (pH 6.1 or 7.4), the IC50 values were 5.3 microM and 19 microM, respectively. The inhibitory action of LEM was not competitive with respect to K+ and was not reversed by dilution, suggesting that the inhibitory action is irreversible. Inhibition of the enzyme activity by LEM was not found when beta-mercaptoethanol (0.1 mM) was premixed with enzyme before addition of LEM, and it was partially recovered by addition of beta-mercaptoethanol or dithiothreitol (50 mM) after LEM treatment. These results suggest that LEM reacts with essential SH groups of H+,K(+)-ATPase and inactivates the enzyme by forming a covalent disulfide bond. The inhibitory activity of LEM was more potent at pH 6.1 than at pH 7.4, and the rate of the reaction of LEM with GSH was enhanced by lowering the pH of the medium. The inhibition of proton transport by LEM (30 microM) was found after the intact vesicles were fully acidified. LEM also strongly inhibited the valinomycin-stimulated H+,K(+)-ATPase activity. Therefore, it is considered that LEM inhibits H+,K(+)-ATPase activity by an unknown activated reaction under the acidic condition. Alternatively, the possibility was also suggested that an acidic condition is not always necessary for the inhibition of H+,K(+)-ATPase activity by LEM, since LEM, at higher concentration, inhibited the initial rate of acidification and inhibited nigericin-stimulated H+,K(+)-ATPase activity in intact vesicles.

Animals↗
PubMed1994

[Effect of a new antiulcer drug, leminoprazole, on the gastric mucosal H+,K(+)-ATPase activity in rats].

The inhibitory action of leminoprazole on the activity of rat gastric mucosal H+,K(+)-ATPase was investigated in vitro and ex vivo. Leminoprazole and omeprazole concentration-dependently inhibited the H+,K(+)-ATPase activity, and their IC50 values were 31 microM and 24 microM, respectively, at pH7.4. Leminoprazole dose-dependently inhibited the H+,K(+)-ATPase activity at 3 and 6 hr after the administration at 10-100 mg/kg, p.o. Leminoprazole (60 mg/kg, p.o.) inhibited the H+,K(+)-ATPase activity persistently, and the duration of its inhibitory action was much longer than that of omeprazole (30 mg/kg, p.o.). In pylorus-ligated rats, good correlations between the respective inhibitory rates against gastric acid output and H+,K(+)-ATPase activity was found after the administration of leminoprazole. These results suggest that leminoprazole inhibits the gastric acid secretion by its ability to inhibit the H+,K(+)-ATPase activity in rats; its inhibitory activity was comparable to that of omeprazole. In addition, leminoprazole (100 mg/kg) inhibited the H+,K(+)-ATPase activity even when administered intragastrically after pylorus-ligation, suggesting that this drug can inhibit H+,K(+)-ATPase activity directly from the gastric lumen. Moreover, leminoprazole (100 mg/kg, p.o.) when administered repeatedly for 2 or 4 weeks inhibited the H+,K(+)-ATPase activity to the same degree as the single administration.

Animals↗
PubMed1994

Effects of NC-1300-O-3 on gastric mucus secretion and prostaglandin release in rats.

We investigated the effect of NC-1300-O-3 on gastric mucus secretion and prostaglandin release into the gastric lumen in rats. NC-1300-O-3 following single or repeated administration for up to 4 weeks significantly increased the hexose content in the gastric lumen at 10 to 100 mg/kg, p.o. Omeprazole and cimetidine at doses that strongly inhibited gastric acid secretion had no effect on the hexose content following single or repeated administration for 8 days. When administered repeatedly for 8 days, NC-1300-O-3, omeprazole and cimetidine significantly decreased the hexosamine content in gastric surface mucosa, but significantly increased gastric mucus secretion was observed at the same time only with NC-1300-O-3, indicating that this agent has a profile of action on gastric mucus metabolism different from those of omeprazole and cimetidine. NC-1300-O-3 at 10 and 30 mg/kg, p.o. and omeprazole at 30 mg/kg, p.o. increased the release of prostaglandins into the gastric lumen, and this was markedly inhibited by pretreatment with indomethacin, suggesting that these agents may enhance prostaglandin biosynthesis in the gastric mucosa. From these results, it seems that the enhancement of NC-1300-O-3 on gastric mucus secretion and prostaglandin biosynthesis in the gastric mucosa contribute to the antiulcer effect of NC-1300-O-3.

Animals↗
PubMed1994

Cytoprotective effect of NC-1300-O-3 against gastric lesions induced by necrotizing agents in rats.

The cytoprotective effect of NC-1300-O-3 and its mechanism of action were investigated. NC-1300-O-3 at doses of 3 and 10 mg/kg, p.o. significantly prevented the formation of gastric lesions by HCl.ethanol in rats, and its efficacy was not influenced by repeated administration for up to 4 weeks. The interaction between NC-1300-O-3 and necrotizing agents in the stomach, which is considered to be related to the development of cytoprotection, was not observed. A preventive effect of NC-1300-O-3 against gastric lesions was observed at the same dose even when gastric secretion was completely inhibited by pretreatment with omeprazole. This suggests that the cytoprotective effect of NC-1300-O-3 is an action on the gastric mucosa independent of its antisecretory effect. The cytoprotective effect of NC-1300-O-3 was not affected by pretreatment with indomethacin but was partly decreased by N-ethylmaleimide pretreatment, suggesting the participation of endogenous sulfhydryl compounds in the action of NC-1300-O-3. This compound dose-dependently increased the hexosamine content in the gastric lumen in rats at a dose range of 3-30 mg/kg, p.o. and slightly inhibited a reduction in surface mucus and mucosal hexosamine content caused by necrotizing agents. Moreover, NC-1300-O-3 at doses of 10 and 30 mg/kg, p.o. significantly inhibited the increased gastric vascular permeability caused by alcohol treatment; and at 30 mg/kg, p.o., it inhibited the reduction in potential difference caused by aspirin in rats. These actions were suggested to contribute to the cytoprotective effect of NC-1300-O-3.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

[Serum IgA-fibronectin complex in children with various renal diseases].

IgA-Fibronectin complex (IgA-FN) has been found in the circulation of patients with IgA nephropathy (IgAN). It has been suggested that circulating IgA-FN is related to IgA deposits in the mesangial area following mesangial matrix expansion in IgAN. We investigated serum IgA-FN in patients with various renal diseases, and examined the relationship between IgA-FN and the clinico-pathological findings. Serum IgA-FN level was measured by enzyme-linked immunosorbent assay (ELISA) in 35 patients with IgAN, 20 patients with Henoch-Schönlein purpura nephritis (HSPN), and other various renal diseases in children. IgA-FN in patients with IgAN was significantly higher than in healthy subjects and patients with minimal change nephrotic syndrome. However some patients with membranoproliferative glomerulonephritis and lupus nephritis had a high level of IgA-FN. The increase in IgA-FN was correlated with macroscopic hematuria and the degree of proteinuria and mesangial matrix expansion in IgAN. Thus, we concluded that the level of IgA-FN is associated with mesangial matrix expansion.

Adolescent↗
PubMed1993

The Goodpasture antigen: common epitopes in the globular domains of collagen IV.

To determine the nature of Goodpasture antibody-reactive epitopes on the globular domains of collagen IV [non collagenous (NC) domain], Goodpasture antigen was characterized by immunochemical and immunohistological techniques using affinity-purified (AP) Goodpasture autoantibodies. Affinity purification of Goodpasture autoantibodies toward alpha 1(IV), alpha 2(IV), and alpha 3(IV) NC domains was performed and revealed antigenic cross-reactivity with all alpha(IV) NC domain subunits, which was confirmed by inhibition ELISA. Since by immunofluorescent microscopy all 3 AP Goodpasture antibodies only stained the central portion (lamina densa) of bovine glomerular basement membrane, it appears that there are common epitopes reactive with Goodpasture autoantibodies present on alpha 1(IV) NC, alpha 2(IV) NC, and alpha 3(IV) NC domains.

Animals↗
PubMed1992

Synthesis and structure-activity relationships of substituted 2-[(2-imidazolylsulfinyl)methyl]anilines as a new class of gastric H+/K(+)-ATPase inhibitors. II.

A series of 2-[(2-imidazolylsulfinyl)methyl]anilines (2) having various substituents on their imidazole and aniline rings was synthesized and examined for their H+/K(+)-ATPase (adenosine triphosphatase) inhibitory effects and antisecretory activity against histamine-stimulated gastric acid secretions in Heidenhain pouch dogs. Although substitutions on the imidazole ring did not enhance biological activity, substitutions on the aniline ring by electron-donating substituents potently enhanced the enzyme inhibitory activity and also showed an inhibitory effect on histamine-stimulated gastric acid secretion after oral administration. In particular, the in vitro activity of the dimethyl (2u--w) and trimethyl (2ac) derivatives was about 10 times that of omeprazole. Also, 4-methyl (2k), 4-methoxy-5-methyl (2y) and 3,5-dimethyl-4-methoxy (2ab) derivatives showed a potent antisecretory effect of more than 80% after oral administration at 6 mg/kg. Although these aniline derivatives have relatively low stabilities in aqueous solution, replacement of the isobutyl group at the aniline nitrogen atom with N-(2-methoxyethyl) group enhanced the stability.

Adenosine Triphosphatases↗
PubMed1992

Partial protein sequence of the globular domain of alpha 4(IV) collagen chain: sites of sequence variability and homology with alpha 2(IV).

The globular domain (NC) of alpha 4(IV) collagen chain was partially sequenced and compared with the NC domain of other collagen IV chains. The alpha 4(IV) NC domain was found to be most closely related to alpha 2(IV) NC domain but distinct from the NC domain of alpha 1(IV), alpha 2(IV), alpha 3(IV) and alpha 5(IV) collagen chains. Partial sequence, representing nearly one half of alpha 4(IV) NC domain, shows 56%, 69%, 51% and 54% identity with the corresponding NC domains of alpha 1(IV), alpha 2(IV), alpha 3(IV) and alpha 5(IV) collagen chains, respectively. A short, highly polar, region of variable sequence is found near the carboxy terminus of alpha 4(IV) NC domain. This sequence corresponds to a non-conserved region among NC domains, suggesting functional specialization at this site. It exhibits high surface probability with predicted structural differences among NC domains. These results confirm uniqueness of alpha 4(IV) NC domain and indicate its structural relatedness to other NC domains of collagen IV.

Amino Acid Sequence↗
PubMed1992

[A structure of ordering and display system by adopting computer for receipt in a medical clinic].

Online and display system for the result of laboratory examination were constructed by adopting a computer for receipt. The computer for receipt was expanded to a new schedule file and a management schedule file. Consequently, reservation system of medical clinic was made and check seats of order decreased in number. It was considered that patients can understand conditions of their illness and results of laboratory examination very easily with this system.

Clinical Laboratory Information Systems↗
PubMed1991

Synthesis and structure-activity relationships of N-substituted 2-[(2-imidazolylsulfinyl)methyl]anilines as a new class of gastric H+/K(+)-ATPase inhibitors.

A series of N-substituted 2-[(2-imidazolylsulfinyl)methyl]anilines (3) was synthesized and evaluated for its biological activity against gastric H+/K(+)-ATPase prepared from rabbit stomach and gastric acid secretions in Heidenhain pouch dogs. Monoalkyl substituents on the nitrogen atom of the aniline moiety markedly inhibited the enzyme activity to the same degree as omeprazole, a representative H+/K(+)-ATPase inhibitor. Most of these compounds, administered at 3 mg/kg i.v. inhibited histamine-stimulated gastric acid secretion. The inhibitory activity of these derivatives on the enzymes at pH 6.0 was more potent than that at pH 7.4, and was distinctly correlated to stability in aqueous solution at pH 5.0.

Adenosine Triphosphatases↗