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Biomedical subjects

H Kikuchi

Publications and source records attributed to H Kikuchi.

At least 1,045 records · Page 58Linked to original sources
PubMedDate not supplied

Analysis of secretion and expression of platelet-derived growth factor in cultured endothelial cells from stroke-prone spontaneously hypertensive rat.

1. We characterized the endothelial cell-derived growth factors of SHRSP and Wistar Kyoto rats (WKY), respectively and found that platelet-derived growth factor (PDGF)-B chain related growth factor constituted a major portion of the mitogenic activity of the conditioned media of endothelial cells from both animals. There were no remarkable qualitative differences between the endothelial cell-derived growth factors of SHRSP and WKY. 2. Northern analysis revealed that the expression of PDGF-B chain was 2-4-fold enhanced in cultured aortic endothelial cells of SHRSP. This enhanced expression of PDGF-B chain, which may be induced under chronic hypertensive conditions, is suggested to contribute to the increase in endothelial cell-derived growth factors reported in this animal.

3T3 Cells↗
PubMedDate not supplied

Significance of serine proteinase and matrix metalloproteinase systems in the destruction of human articular cartilage.

1. During the destruction of articular cartilage, fibrinolytic enzymes and matrix metalloproteinases (MMP) may contribute to the related pathology. The activities, antigens and messenger RNA (mRNA) levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in articular cartilage were measured in patients with no history of joint diseases (control), those with osteoarthritis (OA) classified into osteophyte-formed site (OS) and weight-bearing site (WS), and in patients with rheumatoid arthritis (RA). 2. The uPA content was higher in WS and RA compared to normal. The PAI-1 content was higher in OS and RA compared to normal. Weight-bearing site patients expressed a high uPA mRNA level but a low PAI-1 mRNA level. Osteophyte-formed site patients expressed a low uPA mRNA level but a high PAI-1 mRNA level. 3. The levels of the MMP and mRNA of tissue inhibitors of metalloproteinases (TIMP) were measured in WS, OS, and RA. In WS, the levels of MMP were high and levels of TIMP mRNA expression low. In OS, the levels of TIMP were high and levels of MMP mRNA were low. In RA, the levels of MMP and TIMP mRNA were high. 4. These findings suggest that regulation of fibrinolysis may play an important role in the matrix of articular cartilage with arthropathy.

Aged↗
PubMedDate not supplied

Ebselen in acute middle cerebral artery occlusion: a placebo-controlled, double-blind clinical trial.

A randomized, double-blind, placebo-controlled trial of ebselen was conducted in patients with complete occlusion of the middle cerebral artery. Ebselen or placebo granules suspended in water (150 mg b.i.d. ) were orally administered within 12 h of onset and continued for 2 weeks. The major end points were the maximum volume of cerebral infarct measured on follow-up computed tomography and the Glasgow Outcome Scale score at 1 month. One hundred and five patients were enrolled in this trial. Although the intent-to-treat analysis of 99 patients (43 given ebselen and 56 given placebo) did not reach statistical significance in reduction of the infarct volume (p = 0. 099), the protocol-compatible analysis of 83 patients with complete occlusion of the middle cerebral artery (34 given ebselen and 49 given placebo) determined a significant reduction using ebselen treatment (p = 0.034). A good outcome was seen in approximately 15% more patients from the ebselen group, but the difference between the 2 groups was not significant (p = 0.129). There was a corresponding significant reduction in the volume of cerebral infarct and an improvement in the outcome of patients who started treatment within 6 h of onset. These findings may suggest that ebselen protected the brain from ischemic damage in the acute stage.

Aged↗
PubMedDate not supplied

Bioactivity of the vascular endothelial growth factor trapped in fibrin clots: production of IL-6 and IL-8 in monocytes by fibrin clots.

The blood coagulation cascade is activated following vascular-wall injury. The serine protease thrombin is the final protease in this cascade that causes the formation of fibrin from fibrinogen. Thrombin also causes the activation of platelets, which are trapped in a fibrin net followed by hemostasis. Platelets gathered into fibrin clots release several growth factors such as platelet-derived growth factor and transforming growth factor beta. In the present study, we demonstrated that the vascular endothelial growth factor (VEGF) could be bound to fibrin clots in the plasma, and that incubation of the endothelial cells with these VEGF-bound fibrin clots induced proliferation of endothelial cells. Thus, it suggests that clot-bound VEGF may play a role in wound healing through the proliferation of endothelial cells and vascular smooth-muscle cells. On the other hand, a noticeable migration of monocytes was observed when they were cultured on dishes in the presence of VEGF-bound fibrin clots. Moreover, peripheral blood monocytes incubated in the presence of VEGF-bound fibrin clots strikingly increased the production of IL-6 and IL-8, demonstrating that VEGF trapped in fibrin clots not only induces proliferation of human umbilical vein endothelial cells and migration of monocytes but also enhances secretion of IL-6 and IL-8. Thus, our data suggest that fibrin clots that contain several growth factors act as a bioactive reservoir and may play an important role in hemostasis as well as wound healing.

Blood Coagulation↗
PubMedDate not supplied

Effects of FL-386 on faecal lipid excretion in humans.

A newly synthesized inhibitor of pancreatic lipase and micelle formation, FL-386, was administered at a dose of 400 mg (in the diet, for seven consecutive days) to nine healthy adult volunteers, and changes in faecal mass, frequency of defaecation, and properties of the stools were observed. High performance liquid chromatography and gas-liquid chromatography were used to analyse the faeces for short-chain carboxylic acids, neutral sterols, bile acids, fats and hydroxyfatty acids. FL-386 had little effect on the amounts and composition of short-chain carboxylic acids, neutral sterols, and bile acids excreted, nor did it produce changes in the composition of fatty acids, or the percentages of hydroxyfatty acids in the stool. However, in those patients treated with FL-386, the faecal mass was increased, and stools were softer and contained increased amounts of fatty acids. The compound did not produce particularly fatty stools. It was concluded that FL-386 induces slight disturbance in the digestion and absorption of dietary lipids.

Adult↗
PubMedDate not supplied

Effect of an alpha-glucosidase inhibitor on intestinal fermentation and faecal lipids in diabetic patients.

Eight non-insulin-dependent diabetes mellitus patients, in whom oral hypoglycaemic agents were not effective, were treated with an alpha-glucosidase inhibitor, AO-128 (0.9 mg/day) for 6 months. After 6 months of treatment there was a statistically significant decrease in the blood glucose level 1 and 2 h postprandially. The 2 h blood glucose level was also significantly reduced after 2 months' treatment. The insulin and HbA1c levels after 2 and 6 months' treatment were lower than those before administration. Faecal weight, the frequency of bowel movements, the ratio of hydroxy fatty acids to total fatty acids, and faecal short-chain carboxylic acid content were all increased significantly during treatment. The initially hard stools became normal or soft, although no actual diarrhoea developed. Both faecal bile-acid excretion and the ratio of primary bile acids to total bile acids were increased significantly after 2 months, but they showed some recovery towards the pretreatment levels after 6 months' treatment. There was no distinct change in neutral sterol and fatty acid excretion. Breath hydrogen excretion showed a slight increase after treatment. These results suggest that intestinal fermentation was promoted and the intestinal transit time was shortened by AO-128 administration.

Adult↗
PubMedDate not supplied

Effects of pancreatic digestive enzymes, sodium bicarbonate, and a proton pump inhibitor on steatorrhoea caused by pancreatic diseases.

Forty-five patients with pancreatic steatorrhoea (27 with calcified pancreatitis, 13 with non-calcified pancreatitis, two with pancreaticoduodenectomy, one with total pancreatectomy, and two with pancreatic cancer) were divided into four groups and given the following medication for 2 to 4 weeks: 4 to 6 g/day of sodium bicarbonate (group I); 9 g/day of high-lipase pancreatin (lipase, 56,600 U/g, Fédération Internationale Pharmaceutique (FIP); group II); 12 to 24 tablets or 9.0 g of commercial pancreatic enzyme preparations (group III); or 50 mg of omeprazole (group IV). Faecal fat excretion was evaluated before and after drug administration. Faecal fat excretion was reduced by 2.9 g (range, 1.7 to 5.0 g) in group I; 8.8 g (range, 2.9 to 39.9 g) in group II; 10.8 g (range, 2.3 to 21.8 g) in group III; and 4.3 g (range, 3.6 to 5.6 g) in group IV. The pancreatic digestive enzyme preparation was more effective than sodium bicarbonate and agents that raise the pH of the upper small intestine (such as proton-pump inhibitors) in reducing faecal fat excretion. The results indicate that all of the preparations used are effective against mild pancreatic steatorrhoea. If the condition is more advanced, however, a massive dosage of pancreatic digestive enzyme and possibly the combined use of an agent to raise the pH of the upper small intestine are likely to be effective.

Adult↗
PubMedDate not supplied

Faecal triglycerides and fatty acids in the differential diagnosis of pancreatic insufficiency and intestinal malabsorption in patients with low fat intakes.

To investigate possible parameters for the differential diagnosis of steatorrhoea in patients with low fat intakes, faecal specimens were analysed from 15 patients with steatorrhoea due to chronic pancreatitis and seven patients with steatorrhoea due to intestinal malabsorption. The fat intakes of the patients ranged from 30.1 to 60 g, less than the average in American and European patients. The group with pancreatic steatorrhoea showed a significantly lower faecal output than the group with intestinal steatorrhoea but the two groups did not differ significantly in their total faecal fat excretion or concentration. The percentage triglycerides and the molecular ratio of triglycerides to fatty acids in the faeces were significantly higher (P < 0.01) in the group with pancreatic steatorrhoea than in those with intestinal steatorrhoea. The molecular percentage ratio of triglycerides to fatty acids was 6.8 +/- 2.2 for the chronic pancreatitis group and 2.4 +/- 1.0 for the intestinal malabsorption group; while the respective faecal hydroxy fatty acid contents were 3.1 +/- 3.6% and 10.1 +/- 3.3% (means +/- SDs). These latter two parameters appeared to be the most valuable for distinguishing the two forms of steatorrhoea.

Adult↗
PubMedDate not supplied

Characterization and tissue distribution of liposomes containing lactose mono-fatty acid derivatives.

In this study we characterized liposomes containing the synthetic glycolipids, lactose mono-fatty acid esters (LFEs), whose structures were the most simple ones compared to the other synthetic glycolipids. Gel filtration chromatography was used to confirm that 78 per cent of lactose monostearic acid ester (LSE) or 85 per cent of lactose monoarachidic acid ester (LAE) existed in the liposomal fraction. The size distribution of liposomes containing LFEs was similar to that of the control liposomes which did not contain LFEs. Liposomes containing LFEs were aggregated by Ricinus communis agglutinin from caster bean (RCA120) while the control liposomes were not, with the agglutinability of the liposomes containing LAE being greater than that of those containing LSE. These findings therefore suggested that the LFEs were incorporated into the liposomal membrane with the galactose residues exposed to the outer aqueous phase. Next, the tissue distribution of liposomes containing LAE at 30 min after intravenous administration was compared to that of the control liposomes in rats. Hepatic uptake was 2-fold higher than that of the control liposomes. These results thus demonstrate that liposomes containing LFEs represent potential drug carriers to the liver.

Animals↗
PubMedDate not supplied

Selective uptake of liposomes containing lactose mono-fatty acid derivatives by hepatic parenchymal cells.

In this study we investigated the hepatic uptake of liposomes containing a novel synthetic glycolipid, lactose mono-arachidic acid amide (LAA). Liposomes containing LAA were aggregated by Ricinus communis agglutinin from caster bean, while the control liposomes were not, and the results suggested that the galactose residues of LAA were exposed to the outer surface of the liposomes. Next, the blood clearance and hepatic uptake of liposomes containing LAA after intravenous administration were compared with those of the control liposomes in rat. Hepatic uptake of liposomes containing LAA was greater than that of the control liposomes, rising significantly with dose. As a result of separation of the parenchymal and non-parenchymal cells, it was shown that the increase in hepatic uptake was mostly accounted for by a greater uptake by parenchymal cells. The inhibitory activity of asialofetuin on the hepatic uptake of liposomes containing LAA suggested that a galactose-specific recognition is involved in this uptake. These results demonstrate that the lactose mono-fatty acid amides (LFAs) are promising novel compounds for the introduction of carbohydrate residues onto the liposomal surface and that liposomes containing LFAs are potential carriers for the selective delivery of drugs to specific cells.

Amides↗
PubMedDate not supplied

Distribution of liposomes containing mannobiose esters of fatty acid in rats.

The biodistribution of liposomes modified by mannobiose residues was studied in rat. The purpose of the modification was to target the liposomes to macrophages. Mannobiose mono arachidic acid esters (MAEs) were synthesized and used to modify the surface of liposomes. It was shown by gel permeation chromatography that the MAE was preferentially incorporated into the membrane of the liposomes. After intravenous administration, mannobiose-modified liposomes were eliminated from the systemic circulation more rapidly than control liposomes without the modification. Whilst the modification did not affect the distribution of liposomes to kidney, lung, or thymus, it increased the distribution to liver and spleen. The uptake in the hepatic parenchymal cell fraction was not influenced by MAE incorporation. Taking into account the fact that endothelial cells do not take up particles whose size is > 100 nm, the increase in the distribution to liver were ascribed to an increase in uptake by Kupffer cells. These results suggest that mannobiose mono fatty acid esters are useful in the targeting of liposomes to Kupffer cells and other macrophages.

Animals↗
PubMedDate not supplied

[A case of subacute necrotizing lymphadenitis complicated with brachial plexus neuritis].

A 22-year-old female noted a low grade fever and swelling of the cervical lymph nodes in May 1997, and later developed a dry cough. She was diagnosed to have interstitial pneumonitis, and then administration of corticosteroids alleviated her symptoms. On February 6, 1998, however, a high fever recurred and her swollen cervical lymph node on the right side was biopsied on February 9, 1998. A histological examination revealed an increased number of histiocytes and karyorrhexis of the lymphocytes in the paracortical areas, and she was therefore diagnosed to have histiocytic necrotizing lymphadenitis. She could not fully elevate her arm on February 16, 1998. On admission, her cervical lymph node was swollen on the left side. A neurological examination revealed a marked weakness of the right deltoid muscle, moderate weakness of the right latissimus dorsi, triceps and brachioradialis muscles and also a mild weakness of the serratus anterior, supra- and infra-spinatus, and biceps brachii muscles. The muscle power of the other muscles were normal and no muscle atrophy was evident. Winging of the right scapula was observed. The deep tendon reflexes were normal in all four limbs, and her sensation was also normal. No cerebellar sign was found. The Jackson, Spurling, Allen, Morley and Adson tests were all negative. ESR was mildly elevated to 18 mm/hr, but CRP was negative. RF, ANA and anti-SS-A and SS-B antibodies were positive, whereas LE-test, direct and indirect Coombs tests and other autoantibodies were negative. Needle EMG disclosed fasciculation potentials in the right triceps muscle and polyphasic waves in the right deltoid muscle. MRI showed gadolinium-enhancement of the right brachial plexus. Although an abnormal accumulation of gallium was detected in the right parotid and bilateral submandibular glands, no sicca symptoms were found and the Schirmer test findings were normal. Oral prednisolone (50 mg/day with gradual tapering) alleviated both her symptoms and the gadolinium-enhancement of the right brachial plexus. As a result, her right upper limb paresis was thus considered to have been caused by right brachial plexus neuritis, which was probably associated with histocytic necrotizing lymphadentis. Although acute cerebellar ataxia and meningitis have previously been reported to be complicated with histiocytic necrotizing lymphadenitis, this is the first report to describe the complication of peripheral neuritis with this condition.

Adult↗
PubMedDate not supplied

Diverse biological activities of healthy foods.

Diverse biological activities of 7 healthy foods [powdered pine needle, citrate-fermented sesame, powdered coffee, royal jelly, propolis, pollen and white sesame oil (extracted by super critical state (40 degrees C, 350 atmospheric pressure))] were investigated. The pine needle, sesame and powdered coffee was also extracted successively by ethanol and hot water, and lyophilized. The pine needle and coffee extracts, and propolis showed higher in vitro cytotoxic, bactericidal and oxidation activity, as compared with other 4 lipophilic healthy foods. However, propolis showed slightly lower, but significant cytotoxic and bactericidal activity with much reduced oxidation potential. ESR spectroscopy demonstrated that the cytotoxic activity of these extracts was closely related to their radical generation and O2- scavenging activities. Healthy food components may have both pro-oxidant and anti-oxidant properties. Pre-treatment of mice with pine needle, sesame or powdered coffee extract significantly reduced the lethality of bacterial infection, possibly due to their host-mediated action. These extracts failed to reduce the cytophatic effect of HIV-1 (human immunodeficiency virus) infection in MT-4 cells. No apparent acute toxicity was detected in mice by oral administration of 10 g/kg of these extracts. This data suggest the medicinal efficacy of healthy foods.

Animals↗
PubMedDate not supplied

Combination effect of lignin F and natural products.

We investigated the effect of lignin F, isolated from the alkaline extract of the cone of Pinus parviflora Sieb. et Zucc, on the cytotoxic activity and radical intensity (measured by ESR spectroscopy) of various natural products. Lignin F slightly inhibited the proliferation of human oral tumor cell lines (human squamous cell carcinoma HSC-2, human salivary gland tumor HSG), but not that of human gingival fibroblast HGF, suggesting its tumor specific cytotoxic action. Lignin F enhanced the cytotoxic activity of vitamin K2, vitamin K3, sodium ascorbate (vitamin C), epigallocatechin gallate (EGCG) (a major component of green tea), gallic acid (structural unit of tannin), chlorogenic acid, and 6 tea extracts (Japanese green tea, Japanese barley tea, black tea, Chinese green tea, Chinese Jasmin tea, Chinese Oolong tea), to various extents. On the other hand, lignin inhibited the cytotoxic activity of curcumin and dopamine. ESR spectroscopy demonstrated that combination of lignin and vitamin K3, EGCG or gallic acid synergistically augmented the radical intensity. Lignin F enhanced the bactericidal activity of EGCG against E. coli. These data suggest the beneficial effect of the combination of lignin F and natural products.

Antineoplastic Agents, Phytogenic↗
PubMedDate not supplied

Synergistic cytotoxic action of vitamin C and vitamin K3.

We investigated the combination effect of sodium ascorbate (vitamin C) and menadione (vitamin K3) on the viability of various cultured cells. Human oral squamous cell carcinoma (HSC-2, HSC-3) and human promyelocytic leukemia (HL-60) cells were more sensitive to these vitamins as compared to normal cells (human gingival fibroblast HGF, human periodontal ligament fibroblast HPLF, human pulp cell HPC). The combination of vitamin C and vitamin K3 produced synergistic cytotoxicity against all these 6 cell lines. Treatment with vitamin C or vitamin K3, or their combination, induced internucleosomal DNA fragmentation only in HL-60 cells, but not in the oral tumor cell lines (HSC-2, HSC-3, HSG). ESR spectroscopy showed that vitamins C and K3 produce radicals under alkaline conditions and that the combination of these two vitamins synergistically enhanced their respective radical intensities.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Cerebral hemodynamics in arteriovenous malformations: evaluation by single-photon emission CT.

Cerebral hemodynamics in six patients with supratentorial arteriovenous malformations (AVMs) were studied by using single-photon emission CT with three types of radioactive isotopes: N-isopropyl-p-[123I] iodoamphetamine, 81mKr, and 99mTc-RBC in order to determine the local cerebral blood flow and blood volume associated with these malformations. The AVMs were shown to have high flow while other areas of the brain, including the contralateral hemisphere, had variable areas of diminished perfusion. There was increased blood volume in the regions of AVMs, and poor but evenly distributed blood volume in the other regions. CO2 reactivity during hypocapnia was preserved throughout the brain except for the region of the AVMs. In large AVMs, the ischemic state surrounding the nidus was considered to be caused mainly by the cerebral steal phenomenon.

Adult↗
PubMedDate not supplied

Gas chromatographic determination with electron capture detection of residual ethylene oxide in intraocular lenses.

A sensitive method is described to determine trace quantities of ethylene oxide (EO) in EO-sterilized intraocular lenses (IOLs). An IOL is dipped in ethanol containing 0.25 ppm propylene oxide (PO) in a 4 mL vial, 2 drops of freshly distilled hydrobromic acid is added through a septum, and the mixture is warmed at 50 degrees C for 24 h. It is then neutralized by vigorous shaking with sodium bicarbonate, dehydrated with anhydrous sodium sulfate, and filtered. The filtrate is injected into a gas chromatograph with electron-capture detection, and the peak height ratio of ethylene bromohydrin/propylene bromohydrin is measured. EO residue is calculated from the calibration curve obtained through a similar procedure with the standard EO/PO solutions. The limit of determination is 0.04 microgram/lens (ca 2.0 ppm). When EO residue levels were determined for IOLs sampled at 3 different aeration periods after sterilization, we found that 9 days of aeration was necessary to meet the U.S. Food and Drug Administration proposed limit for EO residue in IOLs.

Chromatography, Gas↗