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Biomedical subjects

K Fujimoto

Publications and source records attributed to K Fujimoto.

At least 505 records · Page 28Linked to original sources

[A case of sarcoidosis associated with severe cardiac conduction disturbances and unilateral pleural effusion].

A 23-year-old man was admitted to our hospital because of non-productive cough. Chest X-ray demonstrated bilateral hilar lymphadenopathy, bilateral infiltration shadows and right pleural effusion. ECG showed complete A-V block and sinus arrest. Transbronchial lung biopsy and pleural biopsy specimens showed non-necrotizing epithelioid cell granulomas. The patient was diagnosed as having sarcoidosis, and was treated with steroid and pacemaker. After steroid therapy, myocardial imaging with thallium-201 showed increase of uptake and the pleural effusion disappeared.

Adult↗

[Effects of succinylcholine on neuromuscular transmission during recovery from vecuronium].

Effects of succinylcholine (SCC), 1 mg.kg-1, given following incomplete recovery from muscle paralysis induced by vecuronium were investigated in 27 female patients undergoing elective surgery, which was performed under epidural anesthesia. Anesthesia was induced with thiamylal 5 mg.kg-1 followed by SCC to facilitate orotracheal intubation. Vecuronium bromide 0.08 mg.kg-1 was given and the lungs were ventilated with 67% N2O in O2 and 0.6% sevoflurane. Neuromuscular function was monitored by means of the induced EMG. The ulnar nerve was stimulated at the wrist. Supramaximal trains of four stimuli (2 Hz for 2 s: pulse width 0.2 ms) were administered every 20 s. The effect of SCC varied depending upon the degree of recovery from vecuronium. At the 25% recovery point, the response to SCC was biphasic, showing an initial reversal followed by an increase of the partial vecuronium block which recovered showing a fade phenomenon on train-of-four stimulation. At the 50% recovery point, an initial reversal was slight. Administered at 75% recovery from vecuronium, SCC produced total neuromuscular blockade without initial recovery. The overall duration of the SCC effect (time from the administration to 90% recovery) was 7-18 min. No prolonged paralysis from SCC occurred.

Adult↗

[Clinicopathological study of 4 patients with idiopathic BOOP, interstitial type on chest X-ray].

We studied four patients with idiopathic Bronchiolitis Obliterans Organizing Pneumonia (BOOP) diagnosed by open lung biopsy. All of four presented with acute onset and a rapid course with progressive dyspnea. Their chest X-ray films showed ground-glass opacities with reduced volumes in the bilateral lower lobes. Their chest CT revealed marked increases in lung density with air bronchograms. Radiologically, it was difficult to distinguish these cases from patients with acute interstitial pneumonia. Histologically, in the uninflated specimens, the collapse of alveoli and alveolar spaces filled with foamy macrophages and proteinous exudates were observed. The organizing tissues were present predominantly in the alveolar ducts, but varied in extent among cases. We considered the reduced lung volumes on chest X-ray films and the marked increases in lung density on chest CT to reflect alveolar collapse. Proliferation of type II pneumocytes was remarkable in all cases, but reactivity to antisurfactant protein-A antibody staining was decreased in the collapsed alveoli. It was suggested that the alveolar collapse was caused, in part, by decreased pulmonary surfactant in addition to obstruction of the alveolar ducts. The rapid responses to of these patients corticosteroid therapy may be due to improvement of the alveolar collapse.

Adult↗

Does the [3H]mepyramine binding site represent the histamine H1 receptor? Re-examination of the histamine H1 receptor with quinine.

Mepyramine is a potent H1 receptor antagonist, and [3H]mepyramine generally is used to label histamine H1 receptors. However, we found that [3H]mepyramine labeled not only the H1 receptor but also a [3H]mepyramine binding protein (MBP) in the liver, which protein appears to be related to the subfamily of debrisoquine 4-hydroxylase (cytochrome P450IID) isozymes. The binding of [3H]mepyramine to the cloned H1 receptor was not affected by 1 microM quinine, an inhibitor of debrisoquine 4-hydroxylase. On the other hand, the binding to MBP in the liver membranes was completely inhibited by 1 microM quinine. These data indicate that the labeling by [3H]mepyramine of H1 receptors and MBP can be completely separated with 1 microM quinine. The majority of [3H] mepyramine binding sites in the cerebral cortex, thalamus and hypothalamus, hippocampus, heart, aorta, lung and spleen were H1 receptors. On the other hand, almost all [3H]mepyramine binding sites in the liver and kidney were MBP. Both H1 receptors and MBP were expressed in the stomach, ileum, cerebellum and adrenal gland. Kd values of [3H]mepyramine for membranes from the cerebellum and stomach in the presence of quinine, which tissues contain both H1 receptors and MBP, approached that value of the cloned H1 receptor. The improved [3H]mepyramine binding assay using quinine is a precise method to characterize H1 receptors by the separate determination of H1 receptors and MBP.

Animals↗

[Intermittent intraarterial infusion chemotherapy using a subcutaneously implanted reservoir in patients with hepatoma].

Hepatocellular carcinomas that should not be treated with transarterial embolization (TAE) were treated with intermittent intraarterial infusion chemotherapy using a subcutaneously implanted reservoir. Among 37 patients, in whom objective evaluation of the initial response was possible, 3 cases of CR, 12 of PR, 10 of NC and 12 of PD were obtained. The response rate was 40.5%. Culminate 1 year survival rates were 80.0% for responders (CR + PR), 4.5% for non-responders (NC + PD) and 35.1% as an average for all patients. The survival in responder patients was better than in non-responders (p < 0.001). To determine the role of this therapy we divided the cases into two groups by anamnesis of TAE and investigated the initial response and prognosis based on the grade of portal vein invasion in each group. In one group of 18 patients, who had not been treated with TAE, there were no relationships between the grade of portal vein invasion and the initial response and between the grade of portal vein invasion and the prognosis. In this group the initial response was better in patients whose one shot infusion chemotherapy immediately before intermittent intraarterial infusion chemotherapy had been effective than in the others. In the other group of 19 patients, who had been treated with TAE, the initial response and prognosis were better in patients with lower grades of portal vein invasion (Vp0-2) than in those with the highest grade (Vp3).

Carcinoma, Hepatocellular↗

[A case of allergic bronchopulmonary fungosis caused by several kinds of fungi].

A 36-year-old man, who had been treated for bronchial asthma since 10 years of age was admitted to Haibara General Hospital because of asthma attack and abnormal chest X-ray shadows. Chest roentgenogram on admission revealed patchy and consolidation shadows in both lung fields. Blood eosinophilia (15%, 1,155/mm3) and elevation of total IgE (7,800 IU/ml) were demonstrated by laboratory examination. Bronchography showed central bronchial ectasia in right B2, B3, B6 and left B1+2, B3 and B6. Investigations of allergy demonstrated elevated specific IgE levels, positive immediate and late skin reactions, positive "dual" asthmatic responses and positive precipitating antibodies for Aspergillus fumigatus, Penicillium luteum and Cladosporium cladosporioides. Aspergillus fumigatus, Penicillium spp. and Cladosporium spp. were cultured from his sputa. From these clinical symptoms and findings of tests of allergy, all three kinds of fungi, Aspergillus fumigatus, Penicillium and Cladosporium, were considered as causative antigens in this case of allergic bronchopulmonary fungosis.

Adult↗

Neuronal histamine in the hypothalamus suppresses food intake in rats.

Using probes to manipulate hypothalamic neuronal histamine, we report here that changes in neuronal histamine modulate physiological feeding behavior in rats. Infusion of alpha-fluoromethylhistidine (FMH), a "suicide" inhibitor of histidine decarboxylase (HDC), into the third cerebroventricle induced feeding in the early light phase when the histamine synthesis was most accelerated. FMH at an optimum 2.24 mumol dose elicited feeding in 100% of rats. Treatment of FMH specifically and selectively decreased concentration of histamine without affecting concentrations of catecholamines in the hypothalamus. Immediately before the dark phase, when the histamine synthesis was normally lower, FMH infusion did not affect feeding-related parameters such as meal size, meal duration or latency to eat. Conversely, thioperamide, which facilitates both synthesis and release of neuronal histamine by blocking presynaptic autoinhibitory H3 receptors, significantly decreased food intake after infusion of a 100-nmol dose into the third cerebroventricle. The effect of thioperamide was abolished with i.p. injection of 26 mumol/kg chlorpheniramine, an H1antagonist. FMH at 224 nmol was microinfused bilaterally into the feeding-related nuclei in the hypothalamus. The ventromedial nucleus (VMH) and the paraventricular nucleus (PVN), but not the lateral hypothalamus, the dorsomedial hypothalamus or the preoptic anterior hypothalamus were identified as the active sites for the modulation. Neuronal histamine may convey suppressive signals of food intake through H1 receptors in the VMH and the PVN with diurnal fluctuation.

Animals↗

[3H]2-(4-phenylpiperidino)cyclohexanol (AH5183) binding to synaptosomes and subcellular fractions obtained from rat brain.

We investigated the binding of [3H]AH5183 (2-(4-phenylpiperidino)cyclohexanol) to rat brain synaptosomes and subcellular fractions. A high content of specific binding was observed in crude synaptosomes obtained from the striatum, cerebral cortex and hippocampus. The highest density of subcellular binding sites was observed in the synaptic vesicle-rich fraction. The affinities of AH5183 binding to crude synaptosomes and the synaptic vesicle-rich fraction were almost equivalent, but the density of binding sites was higher in the synaptic vesicle fraction. The present findings indicate that [3H]AH5183 binding to both synaptosomes and the synaptic vesicle-rich fraction is useful as a cholinergic marker, and that for quantitative studies, binding to the latter fraction is more preferable.

Animals↗

Antitumor agents. 3. Synthesis and biological activity of 4 beta-alkyl derivatives containing hydroxy, amino, and amido groups of 4'-O-demethyl-4-desoxypodophyllotoxin as antitumor agents.

A series of 4 beta-alkyl (7-10), 4 beta-aminoalkyl (12a-y), and 4 beta-amidoalkyl derivatives (14a-g) of 4'-O-demethyl-4-desoxypodophyllotoxin have been synthesized, and their cytotoxicity, inhibition of DNA topoisomerase II (Topo II), and tubulin polymerization were evaluated. All derivatives of 12a-y and 14a-g did not inhibit tubulin polymerization. Many compounds exhibited cytotoxicity and inhibition of Topo II. In particular, 12o, 12s, 12t, and 12u strongly inhibited Topo II (IC50 (microM) 32.5, 60.9, 58.8, and 33.6, respectively) and were strong cytotoxicity against P388 cells (IC50 (M) 1.0, 4.1, 3.3, and 3.0 x 10(-9), respectively), compared with VP-16 (IC50 (microM) 59.2, IC50 (M) 1 x 10(-8), respectively). These compounds were nearly equal to or superior to VP-16 in antitumor activity in vivo (L1210, P388, and Lewis lung) and were more cytotoxic against various human cell lines in vitro than VP-16.

Animals↗

Response characteristics of subthalamic neurons to the stimulation of the sensorimotor cortex in the rat.

Responses of the subthalamic nucleus (STH) neurons to the stimulation of the sensorimotor cortex (Cx) were recorded in intact rats and in those which received lesions in the pallidum, the neostriatum, the brainstem, or the corpus callosum. Most of the STH units (78%) exhibited two excitatory peaks which were interrupted by a brief period of inhibition. Some of units which were located in the peripheral part of the STH tended to lack the brief inhibitory component and exhibited a long period of excitation. These excitations were followed by a long-lasting inhibitory period. Intracellular recording indicated that these responses were EPSPs interrupted by a short IPSP and a long period of disfacilitation of Cx inputs. A quinolinic acid lesion of the neostriatum and a knife cut of the brainstem failed to alter these responses, while an ibotenic acid lesion of the globus pallidus abolished the short inhibition seen in the midst on the excitation. Stimulation of contralateral Cx also evoked excitatory responses in the STH. The responses were completely eliminated by a parasagittal knife cut of the rostral part of the corpus callosum.

Animals↗

Effect of intravenous administration of apolipoprotein A-IV on patterns of feeding, drinking and ambulatory activity of rats.

To characterize the anorectic effect of apolipoprotein A-IV (apo A-IV), we examined the effect of apo A-IV on the patterns of feeding, drinking and ambulation of rats fed ad libitum. A single dose of 200, 135 or 60 micrograms was infused intravenously through a chronically indwelling right atrial catheter just before the dark period. Apo A-IV suppressed food intake by decreasing meal size, but did not affect the interval between meals, the speed of eating, or the latency to eat the first meal after infusion. The anorectic effect of apo A-IV was dose-dependent and was effective for about 3 h after the infusion. The anorectic effect of apo A-IV is specific because inactivation of apo A-IV abolishes its anorectic effect. The anorectic effect of apo A-IV is not shared by apo A-I. Apo A-IV had no effect on drinking behavior or ambulatory activity. The results seem to indicate that apo A-IV specifically decreases the meal size, which supports our hypothesis that apo A-IV may act as a physiological signal for satiation after the ingestion of a lipid meal.

Animals↗

Isolation of the complementary DNA encoding a mouse heparin-binding growth factor receptor with the use of a unique kinase insert sequence.

With the use of reverse transcriptase-polymerase chain reaction techniques focused on a unique kinase insert sequence, the complementary DNA for a mouse tyrosine kinase receptor gene, designated sam3, was isolated from a mouse brain complementary DNA library as a member of the heparin-binding growth factor receptor family or fibroblast growth factor receptor family. The kinase insert region was selected as the probe synthesized by polymerase chain reaction techniques because it composes a unique structure in this receptor family. The sam3 protein, 800 amino acids long, has high homology to mouse K-sam/bek (67%) and N-sam/flg (63%), which we also cloned as the mouse counterparts of human K-sam/bek and N-sam/flg genes, other members of this family. The sam3 protein also has high homology to human FGFR3 (92%) and chicken cek2 (80%) proteins. The sam3 protein is most likely to be a mouse counterpart of human FGFR3 and chicken cek2 proteins. mRNAs of K-sam/bek, N-sam/flg, and sam3/FGFR3 genes were detected in mouse embryo through some adult tissues. The relative amounts of these mRNAs were different depending on the organs examined. Thus, these gene products may have different biological functions in organ development including the central nervous system.

Amino Acid Sequence↗

[Evaluation of the invasion of esophageal cancer to the aorta by cine-MR imaging].

We examined the usefulness of cine-MR imaging for evaluation of the invasion of esophageal cancer to the aorta in 12 cases. We used the technique of field echo pulse sequence. When the low intensity stripe was recognized between the tumor and the wall of aorta, we interpreted it as negative finding of the direct tumor invasion. By using this criteria, 11 of the 12 cases (92%) of the esophageal cancer for aortic wall invasion were correctly diagnosed as compared with 75% correct diagnosis by conventional MR imaging.

Aorta↗

Genomic cloning of the rat histamine H1 receptor.

A rat histamine H1 receptor gene which lacked introns was isolated from a rat genomic library using recently cloned bovine histamine H1 receptor cDNA [Yamashita et al., Proc. Natl. Acad. Sci. USA, 88, 11515-11519 (1991)]. The receptor protein deduced from this isolated gene was composed of 486 amino acids and showed characteristic properties of G protein-coupled receptors. At the 5'-flanking region of the receptor gene, we have located potential TATA box sequences and consensus sequences for the glucocorticoid response element and AP-2 element. After being subcloned into a mammalian expression vector, the isolated gene was transfected to C6 glioma cells. These cells showed significant binding toward [3H]mepyramine. The binding was inhibited by H1 antagonists or histamine. The mode of this binding was comparable to the binding of membranes derived from rat tissues toward [3H]mepyramine. Northern blot analysis detected a 3.0 kb nucleotide band for histamine H1 receptor mRNAs from rat brain and small intestine when these mRNAs were hybridized with the isolated rat H1 gene. The present results demonstrate the isolation of the rat histamine H1 receptor gene.

Amino Acid Sequence↗

Porous polyurethane tubes as vascular graft.

A vascular graft with the inner diameter of about 3 mm was prepared from segmented poly (ether urethane) with an extrusion technique. To make the wall of the vascular grafts porous, NaCl salts were added to the polyurethane solution to be extruded and removed with water extraction after evaporating the solvent in the extruded tube. The wall was reinforced with elastic fiber to prevent dilation. The compliance of the vascular graft measured with the method of Hayashi et al. ranged from 0.2 to 0.3% mmHg -1. The initial Young's modulus was close to that of canine carotic artery, to which the porous polyurethane graft 4-cm long was anastomosed. Vascular grafts were occluded within 2 weeks after implantation, when their pore size was 0, 1.7, or 4.4 mum, whereas those with the pore size of 5.5, 7.4, and 30 mum were patent for longer than 4 weeks. When the vascular graft with the pore size of 30 mum was implanted for 6 months, the luminal surface was covered with neointima, but the endothelium-like cells appearing in the middle of the intima of the vascular graft were immature and sometimes had a very big nucleus. In addition, spindle-shaped, modified smooth muscle cells were noticed in the deep layer of the neointima, especially in the tissue where anastomotic intimal hyperplasia occurred.

Animals↗

Platelet deposition onto polymeric surfaces during shunting.

In an attempt to develop blood-contacting tubes that can be applied for short-term uses with a reduced heparin concentration or, ideally, without heparinization, we evaluated the blood compatibility of polymeric materials with a rabbit ex vivo shunt model. The shunt tubes employed were made of silicone, plasticized poly(vinyl chloride) (PVC), and segmented poly(ether urethane) (PU). In addition, two kinds of surface-modified tube were used: poly(vinyl alcohol) (PVA)-coated PVC and poly(dimethylacrylamide) (PDMAA)-grafted PU. The ex vivo shunt results correlated well with protein adsorption and platelet adhesion in vitro. The following order for the extent of platelet deposition was given, irrespective of the blood-contacting duration: PDMAA-grafted PU < PVA-coated PVC < PU < silicone, PVC. It is likely that many platelet aggregates detached from the PVA-coated PVC surface. For PDMAA-grafted PU, no trace of detachment of aggregates could be detected on any of the SEM photographs. The number and morphology of blood cells adhered onto the tube surfaces during ex vivo shunting were dependent on the kind of polymer surfaces, the blood exposure time, and the flow rate of blood.

Animals↗

Protein adsorption and platelet adhesion onto polyurethane grafted with methoxy-poly(ethylene glycol) methacrylate by plasma technique.

Graft polymerization of methoxy-poly(ethylene glycol) methacrylate, an ester of methacrylic acid and monomethoxy-poly(ethylene glycol) (PEO), was performed onto a polyetherurethane (PU) film and tube under different polymerization conditions by a plasma treatment technique. The surface of grafted PU film was characterized by staining with dye, x-ray photoelectron spectroscopy, contact angle, and zeta potential. All these measurements indicated that water-soluble chains were immobilized on the PU surface, their location being restricted to the film surface region. The PU surface showed reduced protein adsorption in vitro and reduced platelet adhesion in vitro and ex vivo. The optimum graft density suppressing the protein adsorption was as low as 5 micrograms cm(-2). When a small amount of dimethacrylate was added to the monomer solution for graft polymerization to introduce crosslinking in the grafted layer, protein adsorption was further slightly reduced. The extent of reduction in serum albumin adsorption was always less than that of gamma-globulin. Although platelet adhesion was largely reduced by the surface graft polymerization, a definite amount of protein was always adsorbed to the grafted surface.

Adsorption↗