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Biomedical subjects

E Nakamura

Publications and source records attributed to E Nakamura.

At least 91 records · Page 5Linked to original sources
PubMed1996

Photocytotoxicity of water-soluble fullerene derivatives.

New water-soluble fullerene carboxylic acids (1 and 2) derived from C60 and C70 fullerenes, respectively, were examined for photocytotoxicity toward Raji cells (B lymphocyte). These compounds did not show any photocytotoxic effect even at 50 microM, while pheophorbide a showed significant photocytotoxicity at 0.5 microM. Therefore, fullerene derivatives derived from C60 and C70 would not be practical agents for photodynamic therapy.

B-Lymphocytes↗
PubMed1996

Distraction frequency and the gastrocnemius muscle in tibial lengthening. Studies in rabbits.

We compared the effect of various distraction frequencies on the gastrocnemius muscle by evaluating the histological findings, intramuscular enzyme contents, and DNA contents. In 15 rabbits, both tibiae were distracted 1 mm per day. The distraction frequency was 2 steps (0.5 mm/12 hour) by hand on the right side and 120 steps (0.0083 mm/12 minutes) by an auto-distractor on the left. The rabbits were divided into 3 subgroups based on length gain: 10%, 20%, and 30%. Histologically, there were no signs of fibrosis or edema and no differences in the number of necrotic cells, and intramuscular enzyme contents between the 2- and 120-step groups. The DNA content, however, was higher in the 120-step group at 30% lengthening in the middle of the muscle belly, and at 20% and 30% lengthening in the musculotendinous junction. Our findings suggest that an increase in the distraction frequency may promote DNA synthesis in the muscle, thus providing better muscle accommodation during bone lengthening.

Analysis of Variance↗
PubMed1996

[Preclinical and clinical studies on the efficacy of bifonazole in patients with tinea pedis at 10 years after approval. Part 1. Susceptibility to bifonazole of clinical isolates of dermatophytes].

An investigation was carried out to determine whether or not here had been any changes in the susceptibility of clinically isolated strains of Trichophyton metagrophytes and Trichophyton rubrum (both leading causes of tinea) to bifonazole, an imidazole derivative and antifungal for topical use. Susceptibility was measured in 107 strains of these fungi isolated from clinical samples during a study on the treatment of tinea pedis with Mycospor cream in 1995, 42 strains isolated and stored in 1990, and 39 strains isolated and stored prior to development of the drug. The results are as follows: (1) There was no distinct difference in the susceptibility to bifonazole of T. mentagrophytes strains isolated before 1986 and those isolated in 1990 or 1995. (2) T. rubrum strains isolated before 1986 were slightly more susceptible to bifonazole than those isolated in 1995, while the 1990 strains were slightly less susceptible than the 1995 strains, but the difference was not significant. (3) The highest MICs of bifonazole for all the T. mentagrophytes and T. rubrum strains isolated from before 1986 and those in 1995 were relatively low, being 2.5 micrograms/ml and 1.25 micrograms/ml, respectively. These results suggest that no resistance or reduced susceptibility to bifonazole has emerged among clinical isolates of dermatophytes since the development of the drug.

Antifungal Agents↗
PubMed1996

[Fundamental and clinical studies on the efficacy of bifonazole in patients with tinea pedis at 10 years after approval. Part 2. Clinical evaluation].

The usefulness of bifonazole (Mycospor), a topical imidazole antifungal agent approved 10 years ago, was evaluated for the treatment of tinea pedis. Mycospor cream was applied by 141 patients with tinea pedis once daily for 4 233ks, and the clinical efficacy and adverse reactions (as well as any correlations with susceptibility of isolates and the mycological activity of the agent against these isolates) were studied. The results were then compared to those of a previous study. The following results were obtained. 1. Mycological activity Mycological examination results became negative in 63.2% (36/57) of the patients with plantar tinea pedis, in 94.1% (32/34) of those with interdigital tinea pedis, and in 74.7% (68/91) of all tinea pedis patients. 2. Mycological activity and MIC No correlation was found between the MICs of bifonazole against the pathogenic fungi and the rate of eradication on mycological examination. 3. Improvement of symptoms The improvement rates for local symptoms were 82.5% for plantar tinea pedis, 85.7% for interdigital tinea pedis, and 83.7% for all tinea pedis. 4. Clinical efficacy Good clinical efficacies were found in 61.4% of the patients with plantar tinea pedis, in 88.6% of those with interdigital tinea pedis, and in 71.7% of all patients. 5. Safety Regarding adverse reactions, what seemed to be contact dermatitis was reported in 5 out of 127 cases (3.9%). The reaction decreased or disappeared in all cases. 6. Usefulness Mycospor was found to be useful in 64.9% of patients with plantar tinea pedis, in 88.6% of those with interdigital tinea pedis, and in 73.9% of all tinea pedis patients. 7. Comparison with former results The results obtained in the present clinical study were comparable to those obtained in patients with tinea pedis treated in a double-blind comparative study conducted during the development of as a new topical antifungal agent. From the above results, Mycospor cream was confirmed to be still useful, although it has been used widely for the topical treatment of cutaneous mycoses in the past 10 years since its approval.

Adult↗
PubMed1995

Plasma insulin and glucagon responses to acute challenges of acetate, propionate, n-butyrate and glucose in growing gilts (Sus scrofa).

A supraphysiological dose (2.5 mmol kg-1 body weight) of acetate, propionate, n-butyrate or glucose was intravenously injected to measure plasma insulin and glucagon responses in growing gilts. Plasma insulin concentrations remained constant after injection of the volatile fatty acids. Plasma glucagon concentrations increased (P < 0.05) after n-butyrate injection following an initial temporary decrease (P < 0.05), and showed a similar tendency after acetate or propionate injection. These results suggest that a supraphysiological dose of acetate, propionate or n-butyrate may stimulate a plasma glucagon response in growing piglets.

Acetates↗
PubMed1995

In vivo biological behavior of a water-miscible fullerene: 14C labeling, absorption, distribution, excretion and acute toxicity.

BACKGROUND: Water-soluble fullerenes have recently been shown to exhibit considerable in vitro biological activity including cytotoxicity, site-selective DNA cleavage and inhibition of HIV protease. To assess the potential of these compounds as drugs, studies on the in vivo behavior of fullerenes are needed. We therefore set out to synthesize a radiolabeled, water-soluble fullerene, in order to obtain data on the oral absorption, distribution and excretion of this class of compounds. RESULTS: We synthesized a 14C-labeled water-soluble [60]fullerene using dipolar trimethylenemethane, which undergoes cycloaddition to [60]fullerene. When administered orally to rats, this compound was not efficiently absorbed and was excreted primarily in the feces. When injected intravenously, however, it was distributed rapidly to various tissues, and most of the material was retained in the body after one week. The compound was also able to penetrate the blood-brain barrier. Acute toxicity of the water-miscible fullerene was found to be quite low. CONCLUSIONS: Although the water-soluble fullerenes (and possibly their simple metabolites) are not acutely toxic, they are retained in the body for long periods, raising concerns about chronic toxic effects. The fact that fullerenes distribute rapidly to many tissues suggests that they may eventually be useful to deliver highly polar drugs through membranes to a target tissue, however, and they may even have applications in the delivery of drugs to the brain. Recent advances in fullerene synthetic chemistry may also make it possible to control fullerene absorption/excretion profiles in the future.

Administration, Oral↗
PubMed1995

Hepatocellular carcinoma metastatic to the mandible.

A case of hepatocellular carcinoma metastatic to the mandible is described. The patient reported swelling, pain, and trismus after a pathologic fracture. After a systematic examination with the use of 99mTc-methylene diphosphonate, 67Ga-citrate, and 99mTc-pyridoxyl-5-methyl triptophan scintigraphy the primary focus was discovered in the right lobe of the liver. The focus was confirmed by computed tomography and magnetic resonance imaging. The histopathologic diagnosis of hepatocellular carcinoma was made from a biopsy specimen of the mandibular lesion.

Carcinoma, Hepatocellular↗
PubMed1995

Changes in gene expression of pancreatitis-associated protein and pancreatic secretory trypsin inhibitors in experimental pancreatitis produced by pancreatic duct occlusion in rats: comparison with gene expression of cholecystokinin and secretin.

Pancreatic duct occlusion is known to produce a sustained increase in the plasma cholecystokinin (CCK) concentration and to affect the tissue content of CCK in the rat. The tissue content of CCK is correlated with regenerative changes in the pancreas after pancreatic duct occlusion. In the present study, we examined the changes in mRNA levels of pancreatic secretory trypsin inhibitors (PSTIs), pancreatitis-associated protein (PAP), and amylase in the pancreas in comparison with changes in CCK and secretin mRNA levels in the intestine and the histological changes produced by pancreatic duct ligation. Rats with an internal bile fistula and with obstruction of pancreatic flow were prepared and were sacrificed 1, 3, 7, 10, 14, and 28 days later. Then mRNA levels of CCK, secretin, PSTIs, PAP, and amylase were determined by slot-blot analysis. The CCK mRNA level gradually increased to a peak on day 10, was slightly lower on day 14, and returned to the control level on day 28. The level of secretin mRNA did not change. The mRNA levels of PSTIs increased significantly on day 3 after occlusion. PAP mRNA was detectable on days 1 and 3, being maximal on day 1. The mRNA level of amylase was markedly decreased on days 1 and 3, then remained lower than the control level. Histological examination showed acute inflammatory changes in the pancreas on days 1 and 3 and regenerative changes from day 7. These results suggest that a change in gene expression of PAP reflects acute inflammatory changes in the pancreas most sensitively.

Acute-Phase Proteins↗
PubMed1995

Regulation of gene expression of pancreatic secretory trypsin inhibitor-61 and -56 by bile and pancreatic juice in rats.

The rat possesses two pancreatic secretory trypsin inhibitors (PSTI-61 and -56). PSTI-61 has been known to stimulate cholecystokinin (CCK) release, whereas PSTI-56 did not. Both PSTIs are synthesized in the pancreatic acinar cells. CCK has a trophic effect on pancreatic acinar cells, and the exclusion of bile-pancreatic juice from the intestine has been known to be a most potent stimulator of CCK release. In the present study, we examined whether the mRNA levels of PSTI-61 and -56 produced by bile-pancreatic juice diversion were different from each other and compared the changes in CCK mRNA levels in the small intestinal mucosa and the plasma and intestinal CCK concentrations. Male Wistar rats were prepared with internal fistula and bile-pancreatic juice was excluded from the proximal intestine, being introduced into the distal ileum. Rats were sacrificed 1, 3, and 7 days after the operation. The concentrations of plasma and intestinal CCK and the levels of mRNA of CCK in the intestinal mucosa and PSTIs in the pancreas were significantly increased by bile-pancreatic juice diversion. The increase in the mRNA level of PSTI-61 was significantly higher than that of PSTI-56. Administration of CCK antagonist inhibited these changes but administration of CCK agonist could not fully reproduce these changes. These studies suggest that bile-pancreatic juice regulates gene expression of CCK and PSTIs and that the regulatory mechanisms of gene expression of PSTI-61 and -56 may be different.

Animals↗
PubMed1995

Contribution of chromosome 9p21-22 deletion to the progression of human renal cell carcinoma.

To investigate the possible role of genomic aberrations of chromosome 9p21-22 in the tumorigenesis of human renal cell carcinoma (RCC), 10 RCC cell lines, 55 primary RCCs and 5 metastatic lesions were studied by Southern blotting and polymerase chain reaction-based analysis. Nine of 10 RCC cell lines showed a homozygous deletion of MTSI/CDKN2/(p16), while only 1 in 55 primary tumors had this deletion. Loss of heterozygosity on 9p21-22 was observed in 5 of 10 informative primary RCCs from patients with metastasis, but in only 4 of 31 informative tumors (13%) without metastasis (P = 0.025). Futhermore, 3 of 5 metastatic tumors (60%) showed hemi- or homozygous deletion of MTSI/CDKN2. These results indicate that the 9p21-22 deletion may be a relatively late event in RCC tumorigenesis and could be associated with RCC metastasis.

Alleles↗
PubMed1995

Leg lengthening and glycosaminoglycans in the rabbit knee.

We investigated the effects of tibial lengthening by callotasis on glycosaminoglycan (GAG) metabolism of the knee articular cartilage in 30 rabbits. The distraction rate was 1 mm per day. On the right side, the daily distraction was in 2 steps, while on the left it was in 120 steps. The animals were divided into 3 subgroups based on length gain; 10, 20, and 30 percent, respectively. The knee joint fluid and medial tibial cartilage were examined by quantitative analysis of the GAG content and/or synthesis. The immunoreactivity for chondroitin sulfate in the cartilage was also examined by immunohistochemistry. For all length gains, the GAG concentration in the synovial fluid was higher on both sides than in controls, with no difference between sides. The GAG content and synthesis in the cartilage on the 2-step side decreased gradually with increasing length. On the 120-step side, the content did not differ from control values in any length gain, and the level of synthesis at 20 and 30 percent lengthening was higher than the control level. Our findings indicate that the alterations in GAG metabolism are attributable to increased mechanical stress on the articular cartilage, suggesting a moderate increase on the 120-step side compared to an excessive one on the 2-step side.

Animals↗
PubMed1995

Tibial nerve function during tibial lengthening. Measurement of nerve conduction and blood flow in rabbits.

We evaluated in 20 Japanese white rabbits the effects of tibial lengthening on tibial nerve conduction and intraneural blood flow at the end of lengthening. Both tibiae were distracted 1 mm per day. The distraction frequency was in 2 steps (0.5 mm/12 h) on the right side and in 120 steps (0.0083 mm/12 min) on the left. The rabbits were separated into 4 subgroups based on the percentage of lengthening: 0 (control), 10, 20, and 30 percent. In the 2-step group, nerve conduction was delayed at 20 and 30 percent lengthening, compared to the control group, while in the 120-step group, it was delayed only at 30 percent lengthening. Intraneural blood flow in the 2-step group was decreased at 10, 20, and 30 percent lengthenings, while in the 120-step group it was reduced at 30 percent lengthening. Our findings indicate that an increase in the frequency of distraction reduces the impairment of nerve function during bone lengthening.

Animals↗
PubMed1995

Knee cartilage injury after tibial lengthening. Radiographic and histological studies in rabbits after 3-6 months.

We investigated the effects of tibial lengthening by callotasis on the knee articular cartilage in 10 rabbits at 3 and 6 months after distraction. The distraction rate was 1 mm per day, until a 30 percent gain in length. On the right tibia, the daily distraction frequency was in 2 steps by hand, while on the left it was in 120 steps by an autodistractor. 5 animals were killed at 3 months and 5 at 6 months following distraction, and their knee joints were radiographically and histologically examined. On the 2-step side, arthrotic changes at 3 and 6 months after distraction were found in 3 of 5 and 4 of 5 knees, respectively. The severity of change increased with time. On the 120-step side, however, no arthrotic changes were found, except in one knee at 6 months. Our findings suggest that by increasing the frequency of distraction for limb lengthening one can prevent the onset of arthrosis in adjacent joints.

Analysis of Variance↗
PubMed1995

Stimulatory effect of leminoprazole on secretion and synthesis of mucus by rabbit gastric mucosal cells.

We examined whether leminoprazole (an acid pump inhibitor) enhances the secretion and synthesis of gastric mucus in vitro. Mucosal cells were prepared from male rabbit stomachs, and the amounts of secreted and synthesized mucus were determined by the [3H] glucosamine labeling method. Exposure of gastric mucosal cells to leminoprazole at 1 to 100 microM for 8 hr caused significant increases in the secretion and synthesis of mucus in a dose-related manner, but omeprazole was not effective. The stimulatory effects of leminoprazole on secretion and synthesis were observed 4 hr and 6 hr later, respectively. In contrast, both 16,16-dimethyl prostaglandin E2 and nitroprusside, a nitric oxide (NO) generator, caused marked increases in mucus secretion and synthesis even after 2-hr incubation. The effects of leminoprazole on gastric mucus were strongly inhibited by NO synthase inhibitors such as NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine and by the NO scavenger oxyhemoglobin. However, neither indomethacin (an inhibitor of cyclooxygenase), aminoguanidine (an inhibitor of inducible nitric oxide synthase) nor cycloheximide (a protein synthesis inhibitor) could suppress its effects. These results suggest that leminoprazole stimulates the secretion and synthesis of gastric mucus after a lag period, probably through NO produced by constitutive NO synthase.

Animals↗
PubMed1994

Purification, characterization, primary structure, crystallization and preliminary crystallographic study of a serine proteinase from Streptomyces fradiae ATCC 14544.

A proteinase having wide substrate specificity was isolated from Streptomyces fradiae ATCC 14544. This proteinase, which we propose to call SFase-2, was purified from the culture filtrate by S-Sepharose chromatography. The purified enzyme showed an apparent molecular mass of 19 kDa on SDS/PAGE. When synthetic peptides were used as substrates, SFase-2 showed broad substrate specificity. It also hydrolyzed keratin, elastin and collagen as proteinaceous substrates. It was completely inhibited by diisopropylfluorophosphate and chymostatin, but not by tosylphenylalaninechloromethane, tosyllysinechloromethane or EDTA, indicating that it can be classified as a serine proteinase. The matured protein sequence of SFase-2 was determined by a combination of amino acid sequencing and the DNA sequencing of the gene. SFase-2, consisting of 191 amino acids, is a novel proteinase. It showed 76% similarity in the amino acid sequence with Streptomyces griseus proteinase A [Johnson P. and Smillie L. B. (1974) FEBS Lett. 47, 1-6]. For insight into the three-dimensional structure of SFase-2, we obtained single crystals by the vapor diffusion method using sodium phosphate as a precipitant. These crystals belonged to the orthorhombic, space group P2(1)2(1)2(1) with cell dimensions a = 6.92 nm, b = 7.28 nm, c = 2.99 nm; one molecule was present in the asymmetric unit.

Amino Acid Sequence↗
PubMed1994

Intestinal absorption of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue. I. Possible factors for the low oral bioavailability in rats.

Absorption of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue, from the gastrointestinal (GI) tract was evaluated. The bioavailability of this compound after oral administration was considerably poor in rats. Studies were undertaken to elucidate the mechanisms for this low oral bioavailability of azetirelin. The plasma azetirelin levels following intravenous and hepatoportal vein injection were virtually identical over the dose range of 0.02-0.1 mg/kg, indicating a minor contribution of the hepatic first-pass metabolism of this drug. Azetirelin was stable against peptide hydrolases both in luminal fluid and intestinal mucosal homogenates, whereas its degradation occurred when incubated with cecal contents under an anaerobic condition. In addition, complete degradation of azetirelin during the GI transit was disclosed by analyzing the fecal sample collected after oral administration of [14C]azetirelin. These results suggested that gut bacteria may be responsible for the hydrolysis of azetirelin in the GI tract. The low intestinal permeability of azetirelin was revealed by a modified everted gut experiment in various segments of the rat intestine. The poor membrane transport characteristics of azetirelin may be due to its high hydrophilicity. From these results, it was suggested that the insufficient oral bioavailability of azetirelin may be mainly attributed to its low intestinal permeability due to a lack of lipophilicity, and also to the degradation of the peptide by intestinal microflora.

Administration, Oral↗