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Biomedical subjects

M Fujimoto

Publications and source records attributed to M Fujimoto.

At least 361 records · Page 20Linked to original sources

Efficacy of a new quinolone, levofloxacin in patients with surgical infections.

The pharmacokinetics and clinical efficacy of levofloxacin (LVFX, DR-3355), an optically pure S(-)-enantiomer of ofloxacin, were studied in patients after surgery. In the pharmacokinetic study, 4 patients undergoing bile drainage were given 2 100-mg tablets by mouth. Peak levels of LVFX were from 2.22 to 4.02 micrograms/ml of plasma at 2-4 hours after the oral administration, and from 7.5 to 11.3 micrograms/ml of bile at 2-6 hours. Forty-three patients with surgical infections, including 16 skin and soft-tissue infections and 12 wound infections, were treated with LVFX. Twenty-eight (70%) of the 40 patients whose results could be evaluated had excellent or good results; 42 (93%) of the 45 causative organisms identified were eradicated. An episode of diarrhea with chills and fever occurred in a 38-year-old man. The results suggested that LVFX has satisfactory antimicrobial effects in surgical infections.

Adult↗

Neurotrophic factor-like effect of FPF1070 on septal cholinergic neurons after transections of fimbria-fornix in the rat brain.

FPF1070 is an aqueous protein-free solution, which consists of 85% free amino acids and 15% small peptides. Our previous study showed a potent neurotrophic factor-like activity in cultured embryonic cells of dorsal root ganglia. The present study investigated whether FPF1070 regenerated the cholinergic cells in the medial septal nucleus after axonal transections by cutting the fimbria-fornix. Fimbrial transection reduced the number of septal cholinergic cells by 30 +/- 3.6%, compared with the number on contralateral sides at 4 weeks. Intraperitoneal injections of FPF1070 caused 49.9 +/- 6.3% of the cholinergic neurons to survive. Furthermore, the cell sizes of the cholinergic neurons were significantly different: 16.4 +/- 4.2 microns, 14.3 +/- 3.8 microns in FPF1070 treatment and vehicle treatment, respectively. These results indicated that FPF1070 prevents the degeneration and atrophy of impaired cholinergic neurons by systemic administration.

Amino Acids↗

[A patient with liver cirrhosis manifesting various symptoms including cerebellar ataxia due to germanium intoxication].

A patient with hepatitis B virus-associated cirrhosis manifested various symptoms such as anemia, renal damage and neurological signs including cerebellar ataxia due to long-term administration of germanium-containing food. The patient was a 40-year-old male who had taken germanium containing mineral cheese for 26 months after he was diagnosed as having cirrhosis. Twenty four months after beginning to take the mineral cheese, he began manifesting paresthesia of the extremities, dysarthria and gait ataxia. Laboratory findings revealed anemia and renal damage. Biopsy of the peripheral nerve revealed loss of the large sheathed nerve, a characteristic feature of germanium intoxication. A high concentration of germanium (GeO2) was detected in patient's hair and urine. Cerebellar ataxia was characteristic in this patient, which was not reported in the previous papers.

Adult↗

[Zygomatic arch fractures; a neurosurgical viewpoint].

Depressed fractures of the zygomatic arch are often overlooked due to local swelling associated with the injury. However, such fractures are easily detected using roentgenography in superioinferior projection and/or bone image CT examinations of the zygomatic arch. Ten patients with depressed fracture of the zygomatic arch were treated surgically. Nine underwent an operation by the Gillies method within 15 days after the injury and showed good results. In the remaining patient, the operation performed on the 27th day after the injury failed to reconstruct the zygomatic arch perfectly, even when the open procedure was used. The most important point in these cases is the detection and surgical treatment of the fracture at an early stage. Patients with trismus and depressed fracture of the zygomatic arch should be operated on within two weeks after injury. During this period, the surgical method reported by Gillies can be performed easily and also produces successful results.

Adult↗

Gardner syndrome in a boy with interstitial deletion of the long arm of chromosome 5.

We described a 15-year-old boy with Gardner syndrome (GS), mental retardation, and craniofacial abnormalities. High-resolution banding analysis showed an interstitial deletion of the long arm of chromosome 5 (q22.1----q31.1). The breakpoints in the present case and in 3 previously reported 5q- patients with adenomatous polyposis coli suggest that the gene responsible for GS/or familial polyposis coli (FPC) is in the 5q22 region, a result consistent with the findings of linkage studies.

Abnormalities, Multiple↗

Inhibitions of acid secretion by E3810 and omeprazole, and their reversal by glutathione.

A substituted benzimidazole ([4-(3-methoxypropoxy)-3-methylpyridine-2-yl]methylsulfinyl)- 1H-benzimidazole sodium salt (E3810), is a gastric proton pump (H+, K(+)-ATPase) inhibitor. E3810 and omeprazole inhibited acid accumulation dose dependently as measured with aminopyrine uptake in isolated rabbit gastric glands, their IC50 values being 0.16 and 0.36 microM, respectively. The addition of exogenous reduced glutathione (GSH) to the gland suspension reactivated dose dependently the acid secretion which had been inhibited by 2 microM E3810 or omeprazole as a function of the incubation time. Furthermore, GSH at 1 and 3 mM reversed the antisecretory effect of E3810 more quickly than it did that of omeprazole. The antisecretory effect of E3810 was slightly greater than that of omeprazole in histamine-stimulated fistula dogs in vivo. The duration of the antisecretory activity of E3810 at concentrations of 2 and 4 mg/kg was shorter than that of omeprazole at the same concentrations in pentagastrin-stimulated fistula dogs. The reversal of the antisecretory activity of the inhibitors in dogs is suggested to be due to the action of endogenous extracellular GSH, in addition to de novo synthesis of the proton pump, because bullfrog gastric mucosae were found in the present study to secrete GSH into the mucosal solution at the rate of about 0.25 nmol/min/g tissue.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Two states of the L-type Ca2+ channel in PC12 cells: different sensitivity to 1,4-dihydropyridines.

A omega-conotoxin-resistant component of high K(+)-induced [Ca2+]i increase in PC12 cells was further divided into two components by the difference in sensitivity to 1,4-dihydropyridines. The initial phase (up to 30s) was several times less sensitive to 1,4-dihydropyridines than the following plateau phase (several minutes). On the other hand, diltiazem blocked both phases with the same potency. Verapamil also was only a little more sensitive to the initial phase. All four 1,4-dihydropyridines tested showed 5-10 times more potent inhibition of (+)-[3H]PN200-110 binding in PC12 cells under the depolarizing (70 mM K+) condition than under the non-depolarizing (5 mM K+) condition. The biphasic blockade of the high K(+)-induced [Ca2+]i rise by 1,4-dihydropyridines appears to reflect their different affinities under depolarizing and non-depolarizing conditions.

Calcium Channel Blockers↗

Glucocorticoid treatment reduces prostacyclin synthesis in response to limited stimuli.

Dexamethasone 21-acetate (DMS 21-A) time- and dose-dependently suppressed bradykinin-stimulated prostacyclin synthesis in porcine aortic endothelial cells. The suppression was more prominent in the presence of pertussis toxin, which by itself could enhance bradykinin-induced prostacyclin synthesis. The DMS 21-A treatment diminished prostacyclin synthesis also in response to vasopressin. In contrast, it did not affect prostacyclin synthesis in response to arachidonic acid or A23187. Melittin-induced prostacyclin synthesis was reduced only at low doses (1-7 x 10(-7) M). The suppression of bradykinin-induced prostacyclin synthesis by DMS 21-A was completely blocked by cycloheximide. DMS 21-A had no effect on the cellular level of lipocortin I protein, but increased the anti-phospholipase A2 activity in EDTA extracts of the cells. These results suggest that the DMS 21-A treatment induces phospholipase A2 inhibitor protein(s) other than lipocortin I and reduces prostacyclin production in response to limited stimuli.

Animals↗

Protective effect of prostaglandin A2 against menadione-induced cell injury in cultured porcine aorta endothelial cells.

Prostaglandin A2 (PGA2) stimulates the biosynthesis of gamma-glutamylcysteine synthetase and elevates glutathione (GSH) contents in cultured mammalian cells. To clarify the importance of gamma-glutamylcysteine synthetase induction in the defence of endothelial cells against oxidative stress, the effect of PGA2 on menadione (2-methyl-1,4-naphthoquinone)-induced cell injury was examined. Incubation of porcine aorta endothelial cells with menadione produced marked loss of cellular GSH and protein sulfhydryl groups, followed by leakage of lactic dehydrogenase (LDH) into the culture medium. The LDH leakage and modification of protein thiol was, however, completely prevented by pretreatment of the cells with PGA2. The protective effect of PGA2 was more potent than that of cysteine delivery agents such as methionine, N-acetylcysteine or 2-oxo-4-thiazolidine carboxylic acid (OTC). The results suggest that cellular GSH plays an important role in the defence against oxidative stress, and induction of gamma-glutamylcysteine synthetase is effective for protecting vascular endothelial cells.

Animals↗

The effect of K(+)-conductance-blocking substances on the occurrence of retinal spreading depression.

Retinal spreading depression (SD) has been thought to be generated by an abnormal increase in [K+]o in the inner plexiform layer. When a retina isolated from bullfrog was immersed in a medium conditioned for SD (low Cl- Ringer's solution), spontaneous SDs periodically occurred at a fixed interval in the dark. The effect of K(+)-conductance blocking substances (Ba2+, Cs+, TEA and 4-AP) on the occurrence of SD was studied using the concomitant changes in the field potential (spreading depression potential; SDP) as an index. These substances increased the frequency of occurrence and decreased the amplitude of the potential. According to the Müller cell theory of SDP, an increase in [K+]o depolarizes the Müller cells and the resulting extracellular current generates the potential change. Since the small amplitude of the SDP reflects the decreased K+ current, it may be said that the K(+)-buffering capacity of the Müller cells was partially reduced by the substances and that the frequency of the SD occurrence consequently increased in order to clear accumulating [K+]o from neurons with the decreased buffering capacity. The present results lend a good support to the current Müller cell theory for the occurrence of SDP.

4-Aminopyridine↗

The background adaptation of the flatfish, Paralichthys olivaceus.

The background adaptation of the flatfish, Paralichthys olivaceus, was studied by sliding beneath the fish a long strip of plastic sheet with various patterns to serve as a background. The body shade and pattern differed depending upon the pattern used. In general, the fish showed maximal pallor on a white background and darkened when lying on a black background. With a pattern of large checks, several black patches became conspicuous. The fish showed the same tendency in terms of response even when the left eye was covered. However, the fish was prevented from manifesting these changes when the right eye was covered. The results suggest that the left eye of the fish does not see the immediate background. This conclusion is supported by an anatomical study.

Animals↗

Preparation and characterization of labelled interferon-gamma and the development of radioreceptor assay for interferon-gamma.

A 125I-labelled recombinant interferon-gamma (IFN-gamma) was prepared by the lactoperoxidase-glucose oxidase method. The specific activity of the labelled IFN-gamma was 31 Bq U-1 and its molecular weight, immunoreactivity and receptor binding ability remained the same after the labelling. Using the labelled IFN-gamma and FL5(-1) cells from human amniotic membrane, a radioreceptor assay was developed. Natural IFN-gamma, recombinant IFN-gamma and the labelled IFN-gamma were observed to bind to the same binding sites on the cells with similar affinity (Kd = 1.3-2.2 x 10(-10) M). The radioreceptor assay was more specific than a bioassay because the labelled IFN-gamma did not compete with IFN-alpha or IFN-beta. It was much more sensitive (90 pM) than conventional competitive radioimmunoassay (300 pM) using the same labelled IFN-gamma, and as sensitive as immunoenzymometric assay (60 pM). The radioreceptor assay should be useful not only for research on IFN-gamma but also for the determination of biological activity in process control and/or quality control of IFN-gamma manufacturing.

Binding, Competitive↗

A simple and sensitive radioimmunoassay for adenosine.

We developed a simple and sensitive radioimmunoassay (RIA) for adenosine. The RIA is based on the double antibody method with adenosine 2', 3'-0-disuccinyl-3-[125I]-iodotyrosine methyl ester (diSc-adenosine-[125I]-TME) as a tracer. Anti-adenosine antiserum for the RIA was raised in rabbits immunized with diSc-adenosine conjugated to human serum albumin (diSc-adenosine-HSA). All samples and standards were succinylated prior to assay. The present immunoassay allows detection of 6.25-400 pmol/ml of adenosine in sample. Values obtained by the RIA and by a HPLC analysis showed a high correlation with correlation coefficient of 0.997. In order to determine adenosine in plasmas, blood cells must be separated in the presence of 6 mM EDTA, 0.006% dipyridamole (Dip) and 23 microM 2'-deoxycoformycin (dCF) at 2 degrees C. Adenosine in plasma could be accurately determined by the proposed method even without any pretreatments by deproteinizing. The adenosine levels with or without EDTA-treated normal human plasmas determined were 26.2 +/- 7.26 and 100 +/- 3.62 pmol/ml (mean +/- SEM), respectively.

Adenosine↗

An enzyme-linked immunosorbent assay (ELISA) for guanosine 3',5'-cyclic monophosphate (cGMP) in human plasma and urine using monoclonal antibody.

An ELISA for cGMP in human plasma and urine using a monoclonal antibody is described. The monoclonal antibody was raised against succinyl cGMP conjugated to human serum albumin. The conjugate was adsorbed to the ELISA plate, giving an immobilized antigen approach which simplifies subsequent assay procedures. As low as 1.56 fmol/well of both plasma and urinary cGMP is measurable. Recoveries of added cGMP in plasma and urine were from 97% to 105%. Intra-assay coefficients of variation were less than 7.0% for plasma and 7.1% for urine samples. Inter-assay coefficients of variation for plasma and urine samples were less than 9.9% and 9.5%, respectively. The values obtained by ELISA correlated well with those by radioimmunoassay (RIA) (plasma: r = 0.96, n = 50; urine: r = 0.98, n = 60).

Antibodies, Monoclonal↗

An analysis of inputs to ON-OFF amacrine cells in the carp retina with kynurenic acid.

Amacrine cell inputs were studied in the carp retina. Responses to light of bipolar and amacrine cells in off-pathways were suppressed by 0.5 mM kynurenic acid (Kyn), while those in on-pathways were not. In ON-OFF amacrine cells, the sustained potential level during illumination shifted in the depolarizing direction. The depolarizing response elicited in off-center bipolar cells by transretinal current was also suppressed, but those elicited in amacrine cells were not. The results indicated that off-pathways are selectively suppressed by 0.5 mM Kyn at the level of receptor-bipolar synapses and demonstrated that sustained levels of ON-OFF amacrine responses are determined by a balance of inputs from on- and off-center bipolar cells.

Animals↗

Receptors for endothelin in the central nervous system.

The quantitative receptor autoradiographic method we used revealed that specific [125I]endothelin-1 ([125I]ET-1) binding sites are highly concentrated in the choroid plexus (ChP), subfornical organ (SFO), lacunosum molecular layer of the hippocampus (LMol), and granular layer of the cerebellum (GC) of the rat brain. [125I]ET-1 bound to the rat ChP and LMol with a high affinity and to the SFO and GC with a low affinity. The possibility that ET-1 acts as a neuropeptide within the central nervous system by interacting with specific receptors would have to be considered.

Animals↗

Neuropeptide Y receptor in vascular smooth muscle.

125I-Bolton-Hunter (125I-BH) neuropeptide Y (NPY) was used to identify specific high-affinity NPY binding sites in porcine aortic smooth muscle membrane fractions and to characterize the binding sites in comparison with those in porcine hippocampal membrane fractions. Ca2+, but not Mg2+ or Mn2+, enhanced specific 125I-BH-NPY binding in aortic smooth muscle, while all of the cations did in hippocampus. The fast, saturable, and selective binding was to a single population of sites, with a KD of 0.99 +/- 0.11 nM and a Bmax of 0.35 +/- 0.06 fmol/mg protein. GTP and its non-hydrolyzable analogues reduced 125I-BH-NPY binding dose dependently. Neither calcium channel blockers nor noradrenaline had any effect on the binding. Among structurally related peptides, peptide YY displaced 125I-BH-NPY binding as potently as NPY, while human, avian, and rat pancreatic polypeptides displaced 125I-BH-NPY binding 100 times less potently than NPY. The C-terminal fragment NPY(13-36) for inhibiting 125I-BH-NPY binding in aortic smooth muscle was approximately 40 times less potent than in the hippocampus. When we examined the effect of these peptides on cytosolic free Ca2+ ([Ca2+]i) in cultured porcine aortic smooth muscle cells, only the peptides showing high affinity for 125I-BH-NPY binding sites increased [Ca2+]i. These results indicate that the NPY binding sites labeled by 125I-BH-NPY in aortic smooth muscle are functional receptors and have different properties from those in the hippocampus with respect to dependency on divalent cations, sensitivity to GTP analogues, and affinity for NPY(13-36) and pancreatic polypeptides.

Animals↗