Biomedical subjects

M Fujii

Publications and source records attributed to M Fujii.

At least 91 records · Page 5Linked to original sources

PubMed2001

Synthesis and biological properties of DNA-sugar conjugates.

In order to improve the pharmacological properties of antisense and antigene oligonucleotides, oligodeoxynucleotides conjugated with amino sugars at the 5'-terminus were synthesized by solid phase fragment condensation (SPFC) method. The obtained DNA-sugar conjugates were evaluated in their chemical and biological activities to show that 5'-end modification of oligonucleotides with sugars enhanced the thermal stability of the hybrid duplex with complementary DNA, the resistance against nuclease digestion and the membrane permeability of the conjugates.

Amino Sugars↗

PubMed2001

Synthesis and biological properties of DNA-peptide conjugates.

Some naturally occurring nuclear localizing signals (NLSs) and some artificially designed peptides were covalently conjugated by solid phase fragment condensation (SPFC) method. These DNA-peptide conjugates showed enhanced permeability into cells as well as enhanced hybrid stability with ssDNA and dsDNA, and also higher resistance against nuclease digestion.

Base Sequence↗

PubMed2001

Argon plasma surgery for the inferior turbinate of patients with perennial nasal allergy.

OBJECTIVES: Argon plasma coagulation (APC) is a new electrosurgical modality. The advantages of APC are coagulating of the target tissue without contact and the creation of uniformly deep devitalized and coagulated zones. The objectives of the present study were to determine the clinical effects of APC for the inferior turbinate of patients with nasal allergy and to clarify the histological changes in the mucosa after APC. STUDY DESIGN: In a prospective study, 95 patients with perennial nasal allergy were treated with APC. Nasal symptoms and intranasal findings were evaluated preoperatively and 1, 3, and 6 months, and 1 year after the APC. Mucosal specimens from the turbinates were examined under light and electron microscopy. RESULTS: Nasal stuffiness was improved in 77 of 79 (97.5%) patients after 1 month, in 50 of 51 (98.0%) patients after 3 months, in 20 of 23 (87.0%) patients after 6 months, and in 9 of 12 (75.0%) patients at 1 year after the APC. Rhinorrhea was improved in 46 of 75 (61.3%) patients after 1 month, in 40 of 51 (78.4%) patients after 3 months, in 16 of 21 (76.2%) patients after 6 months, and in 6 of 10 (60.0%) patients at 1 year after the APC. The sneezing was improved in 32 of 54 (59.3%) patients after 1 month, in 21 of 35 (60.0%) patients after 3 months, in 10 of 14 (71.4%) patients after 6 months, and in 6 of 8 (75.0%) patients at 1 year after the APC. In the intranasal findings, congestion of the inferior turbinate improved in 75 of 76 (98.7%) patients after 1 month, in 49 of 52 (94.2%) patients after 3 months, in 20 of 23 (87.0%) patients after 6 months, and in 7 of 11 (63.6%) patients at 1 year after the APC. The nasal discharge was reduced in 40 of 75 (53.3%) patients after 1 month, in 32 of 52 (61.5%) patients after 3 months, in 15 of 22 (68.2%) patients after 6 months, and in 5 of 11 (45.5%) patients at 1 year after the APC. No patients needed nasal packing after the APC. CONCLUSIONS: This is the first report on the clinical effects of turbinate surgery for nasal allergy using APC. APC was useful fer turbinate surgery of nasal allergy, especially for nasal stuffiness and congestion of the turbinate.

Adolescent↗

PubMed2001

Structural studies on C-amidated amino acids and peptides: structures of hydrochloride salts of C-amidated Ile, Val, Thr, Ser, Met, Trp, Gln and Arg, and comparison with their C-unamidated counterparts.

To elucidate the structural features of amino acids caused by the C-terminal alpha-amidation, the crystal structures of HCl salts of C-terminal amidated Ile, Val, Thr, Ser, Met, Trp, Gln and Arg were analysed and compared with those of their C-terminal free acids. The bonding parameter of the amide group was little affected by the different chemical properties of the side chains. As for the molecular packing patterns, some structural differences were observed by the C-amidation. The Calpha-H...O hydrogen bonds and carbonyl-carbonyl interactions were more strengthened by the salt formation with HCl in C-amides than C-acids. Furthermore, there is a clear difference between the interaction patterns with Cl ions. In most C-amide crystals, Cl ions are bifurcately hydrogen-bonded to two neighbouring amide NH(2) groups and the parallel layers of the C-amides and Cl ions are alternatively formed. In the case of the carboxyl OH in C-acid crystals, however, the direct hydrogen bond with the Cl ion is not always observed and is largely dependent on the crystal packing environment. This suggests the superior hydrogen-bonding ability of NH...Cl(-) compared with OH...Cl(-). The difference in hydrogen-bonding ability between the amide and carboxyl groups is considered, based on the spatial dispositions of the hydrogen-bonding polar atoms/groups.

Amides↗

PubMed2001

The citrus flavonoid, nobiletin, inhibits peritoneal dissemination of human gastric carcinoma in SCID mice.

The flavonoid nobiletin (5,6,7,8,3',4'-hexamethoxyflavone), found in Citrus depressa Rutaceae, a popular citrus fruit in Okinawa, Japan, reportedly inhibits the production of pro-matrix metalloproteinase (proMMP)-1, 3, and 9 in rabbit synovial fibroblasts in vitro. In the present study, we demonstrated the inhibitory effects of nobiletin on the proliferation of the cancer cell line, TMK- 1, and its production of MMPs. In the SCID mouse model, we found that nobiletin inhibited the formation of peritoneal dissemination nodules from TMK-1. The enzymatic activity of MMP-9 expressed in culture medium obtained from a co-culture of TMK-1 and mouse fibroblastic cells was inhibited by nobiletin in a concentration-dependent manner. In the SCID mouse model, total weight of dissemination nodules was significantly lower in the treated group compared with the vehicle control group (0.07 g vs. 0.78 g, P = 0.0059). The total number of dissemination nodules was also significantly lower than in the vehicle control group (7.5 vs. 69.3 / body, P = 0.0001). These results suggest that nobiletin may be a candidate anti-metastatic drug for prevention of peritoneal dissemination of gastric cancer.

Animals↗

PubMed2001

[A questionnaire survey on the theory of postoperative infection prophylaxis in gynecology].

A questionnaire survey on the theory of postoperative infection prophylaxis was conducted to obtain the consensus on perioperative antimicrobial use among gynecologists in Japan in the period from April to July 2000. Fifty-six of the 83 gynecologists replied, and the following consensus was obtained. An antimicrobial prophylaxis (AMP) agent should be chosen based on their efficacy against the pathogens expected to be contaminants, such as Staphylococcus spp., Escherichia coli and Bacteroides fragilis group. Use an AMP agent that archives a bactericidal concentrations in both the serum and operating site. Use an AMP agent that has little unfavourable side effects. The newer agents should be considered as a therapeutics for postoperative infections. The therapeutic antimicrobial agents having no cross-resistance to the AMP agents should be used, if postoperative infection is suspected or developed. The most commonly used agent for clean operations are cefazolin (CEZ), followed by cefotiam (CTM) and cefmetazole (CMZ). The most commonly used agent for clean-contaminated operations where low grade level of bacterial invasion expected is CTM, followed by CEZ and CMZ, where as operations where mild grade level of bacterial invasion expected is flomxef (FMOX), followed by CTM and other cephalosporins.

Anti-Bacterial Agents↗

PubMed2001

[A questionnaire survey on the theory of postoperative infection prophylaxis in orthopedics].

A questionnaire survey on the theory of postoperative infection prophylaxis was conducted to obtain the consensus on perioperative antimicrobial use among orthopedists in Japan in the period from April to September 2000. Fifty of the 91 orthopedists replied, and the following consensus was obtained. An antimicrobial prophylaxis (AMP) agent should be chosen based on their efficacy against the pathogens expected to be contaminants, such as Staphylococcus spp., and Streptococcus spp., Use an AMP agent that achieves a bactericidal concentration in both the serum and operating site. Use an AMP agent that has little unfavourable side effects. Use an AMP agent that affects minimally the normal bacterial flora. The most commonly used agents are the penicillins and first and second generation cephalosporins. The optimal strategy for most commonly used agents entails infusion of the first dose between approximately 30 minutes pre and post-skin incision and the therapeutic levels should be maintained throughout the operation. The AMP agents having no cross-resistance to the prophylactic agents should be used, if postoperative infection is suspected or developed. The most commonly used agent for both clean operations with or without foreign implants and dirty operations is cefazolin (CEZ), followed by cefotiam (CTM) and flomoxef (FMOX).

Anti-Bacterial Agents↗

PubMed2001

Helicobacter pylori infection and coronary heart disease in Japanese patients.

Although several independent studies have claimed a link between Helicobacter pylori infection and coronary heart disease (CHD), this association has not been established conclusively. The aim was to determine whether an association between H. pylori infection and CHD can be demonstrated in Japanese patients. Three-hundred and four patients who underwent consecutive coronary arteriography were investigated. Ninety-four patients had single-vessel coronary stenosis and 112 had multi-vessel stenosis. The remaining 98 patients had no significant stenosis in any coronary arteries. H. pylori infection was diagnosed serologically and the association between infection and CHD was estimated by the odds ratio. The serum pepsinogen (PG) I-II ratio was used to estimate the degree of gastric atrophy. Seropositivity for H. pylori was significantly higher in the patients with CHD (67%) than in the controls (50%; p = 0.006). The odds ratio for CHD after having H. pylori infection was estimated as 1.35 (95% confidence interval 1.03-1.78; p = 0.028), after adjustment for the common risk factors of CHD in a logistic regression analysis. The association between CHD and H. pylori infection was more significant among patients without any history of diabetes or smoking. The PG I-II ratio in H. pylori-positive patients was significantly higher in the multi-vessel group (3.46) than in the control or single-vessel group (2.86, p = 0.030; 2.78, p = 0.008; respectively). H. pylori infection was shown to be an independent risk factor for CHD in Japanese patients, especially among those who did not have a history of diabetes or smoking. These data imply that the association between H. pylori infection and CHD is clinically relevant.

Adult↗

PubMed2001

cDNA cloning, expression studies and chromosome mapping of human type I serine/threonine kinase receptor ALK7 (ACVR1C).

Transforming growth factor-beta (TGF-beta) superfamily related growth factors signal by binding to transmembrane type I and type II receptor serine/threonine kinases (RSTK), which phosphorylate intracellular Smad transcription factors in response to ligand binding. Here we describe the cloning of the human type I RSTK activin receptor-like kinase 7 (ALK7), an orthologue of the previously identified rat ALK7. Nodal, a TGF-beta member expressed during embryonic development and implicated in developmental events like mesoderm formation and left-right axis specification, was recently shown to signal through ALK7. We found ALK7 mRNA to be most abundantly expressed in human brain, pancreas and colon. A cDNA encoding the open reading frame of ALK7 was obtained from a human brain cDNA library. Furthermore, a P1 artificial chromosome (PAC) clone containing the human ALK7 gene was isolated and fluorescent in situ hybridization (FISH) on metaphase chromosomes identified the gene locus as chromosome 2q24.1-->q3. To test the functionality of the ALK7 signaling, we generated recombinant adenoviruses containing a constitutively active form of ALK7 (Ad-caALK7), which is capable of activating downstream targets in a ligand independent manner. Infection with Ad-caALK7 of MIN6 insulinoma cells, in which ALK7 has previously been shown to be endogenously expressed, led to a marked increase in the phosphorylation of Smad2, a signaling molecule also used by TGF-betas and activins.

Activin Receptors, Type I↗

PubMed2001

Kinematic modeling of jaw-closing movement during food breakage.

It has been demonstrated that the vertical jaw movement trajectories during gum-chewing can be explained by jerk-cost minimization. However, it is uncertain whether the masticatory jaw movement in space can be predicted by the minimum-jerk model. The aims of the present study were to develop minimum-jerk models that would explain 3D masticatory jaw movements with different hardnesses of foods, and to evaluate if the models can predict the movements accurately. The 3D masticatory jaw movement during food breakage was formulated for two types of test foods. The coefficients of determination (R2) between the measured and model-based values ranged from 0.846 to 0.882. Differences were found in the kinematic parameters between the test foods. The results suggest that the models predict the 3D jaw movements during food breakage and are effective in differentiating among the kinematic features of masticatory jaw movements that are peculiar to the mechanical properties of foodstuffs.

Adult↗

PubMed2001

The interaction of somatosensory evoked potentials between mixed-sensory nerves and sensory-sensory nerves.

The interactions between two different nerves occur by occlusion or inhibition when two nerves share the synaptic connections. In our previous study, we have demonstrated that posterior tibial nerve and peroneal nerve sensory inputs interact with each other, i.e., preceding stimulus to one nerve suppresses the somatosensory evoked potential (SEP) of the other nerve when two stimuli are delivered in close sequence. The course of suppression follows two phases; the first one occurring at short interstimulus intervals (ISIs) of the two nerves less than 10 msec, and the second one being at around 30 msec ISI after partial recovery following the first suppression phase. In that study, we have postulated that the second phase suppression was equivalent for the movement induced "gating" mechanism. In this study, the interactions of mixed nerve (posterior tibial) and sensory nerve (sural), and also sensory (sural) and sensory (saphenous) nerves were examined. We found that the mixed nerve (posterior tibial) exerted similar dual phases of suppression (as was seen in posterior tibial--peroneal nerve study) on to the sural nerve SEP, but the reverse was not true. Also the sensory and sensory nerve interactions were not mutually equal; the sural nerve stimulation caused two phases suppression but the reverse condition did not show significant suppression. The above findings suggest (1) interference input from the sensory nerve to the mixed nerve is much weaker than the reverse condition, and (2) sensory and sensory nerves interactions occur but two nerves' interference inputs are not necessarily equal and one could dominant the other.

Adult↗

PubMed2001

Synergistic effects of different bone morphogenetic protein type I receptors on alkaline phosphatase induction.

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta superfamily, which regulate the differentiation of osteoprogenitor cells. Here we show that among members of the BMP family, BMP-4 and growth/differentiation factor 5 (GDF-5) induce osteoblast differentiation through the activation of three receptor-regulated Smads (i.e. Smad1, Smad5 and Smad8). By contrast, BMP-6 and BMP-7 induce alkaline phosphatase activity through Smad1 and Smad5, but not through Smad8. Consistent with these findings, BMP-4 induced phosphorylation and nuclear translocation of Smad1, Smad5 and Smad8, but BMP-6 activated only Smad1 and Smad5. BMP-4 and GDF-5 are known to bind to activin receptor-like kinase 3 (ALK-3) and/or ALK-6 (also termed BMP type IA and type IB receptors, respectively), whereas BMP-6 and BMP-7 preferentially bind to ALK-2. Compared with the effects induced by only one of the type I receptors, the combination of constitutively active forms of ALK-2 and ALK-3 (or ALK-6) more strongly induced alkaline phosphatase activity in C2C12 cells. Moreover, addition of BMP-4 and BMP-6 to C2C12 cells resulted in higher alkaline phosphatase activity than that of only one of these BMPs. The combination of ALK-2 and ALK-3 also induced higher transcriptional activity than either receptor alone. Thus, ALK-2 and ALK-3 (or ALK-6) might synergistically induce osteoblast differentiation of C2C12 cells, possibly through efficient activation of downstream signaling pathways.

Activin Receptors↗

PubMed2001

Preparation of rapidly disintegrating tablet using new types of microcrystalline cellulose (PH-M series) and low substituted-hydroxypropylcellulose or spherical sugar granules by direct compression method.

To decrease the sensation of roughness when a tablet, which is rapidly disintegrated by saliva (rapidly disintegrating tablet), is orally taken, we prepared rapidly disintegrating tablets using microcrystalline cellulose (Avicel PH-M series), a new type of pharmaceutical excipient that is spherical and has a very small particle size (particle size, 7-32 microm), instead of conventional microcrystalline cellulose (PH-102) used in the formulation of tablets containing acetaminophen or ascorbic acid as model drugs for tableting study. Tablets (200 mg) prepared using spherical microcrystalline cellulose, PH-M-06, with the smallest particle size (mean value, 7 microm) had sufficient crushing tolerance (approximately, 8 kg) and were very rapidly, disintegrated (within 15 s) when the mixing ratio of PH-M-06 to low-substituted hydroxypropylcellulose (L-HPC) was 9:1. Sensory evaluation by volunteers showed that PH-M-06 was superior to PH-102 in terms of the feeling of roughness in the mouth. Consequently, it was found that particle size is an important factor for tablet preparation using microcrystalline cellulose. It is possible to prepare drugs such as acetaminophen and ascorbic acid (concentration of approximately 50%) in the tablet form using PH-NM-06 in combination with L-HPC as a good disintegrant at a low compression force (1-6 kN). To solve the problem of poor fluidity in the preparation of these tablets, we investigated the use of spherical sugar granules (Nonpareil, NP-101 (sucrose and starch, composition ratio of 7:3), NP-103 (purified sucrose), NP-107 (purified lactose) and NP-108 (purified D-mannitol)). Rapidly disintegrating tablets can be prepared by the direct compression method when suitable excipients such as fine microcrystalline cellulose (PH-M-06) and spherical sugar granules (NP) are used.

Carbohydrates↗

PubMed2001

Pharmacokinetics of acetaminophen from rapidly disintegrating compressed tablet prepared using microcrystalline cellulose (PH-M-06) and spherical sugar granules.

The aim of the present study was to evaluate the bioavailability of a drug from rapidly disintegrating tablets prepared using fine spherical crystalline cellulose (PH-M-06) and spherical sugar granules (Nonpareil, NP). Rapidly disintegrating tablets containing acetaminophen as the model drug in combination with a mixture of NP-108 (purified n-mannitol) and PH-M-06 were prepared. Plasma concentration profiles and pharmacokinetic parameters of acetaminophen in rabbits were investigated after oral administration of the prepared tablets. No significant difference in Cmax and AUC(0-infinity) of acetaminophen between rapidly disintegrating tablets and conventional tablets was observed after direct administration of these tablets into the stomach of rabbits. However, tmax (15 min) of acetaminophen from rapidly disintegrating tablets was significantly (p<0.05) shorter than that from conventional tablets (130 min). The same tmax was observed for rapidly disintegrating tablets and solution. When suitable excipients such as fine spherical microcrystalline cellulose (PH-M series) and spherical sugar granules (NP series) were used, rapidly disintegrating tablets could be prepared by the conventional direct compression method. According to the results of moment analysis, the mean residence time (MRT) obtained between both rapidly disintegrating and conventional tablets indicates that the mean absorption time (MAT) from these tablets is approximately 60 and 90 min, respectively. This difference in MAT between the two tablets may be caused by the difference in the sum of the mean dissolution time (MDT) and the mean disintegration time (MDIT) of these tablets. Rapidly disintegrating tablets allow rapid absorption of the drug compared with conventional tablets.

Acetaminophen↗

PubMed2001

Vasospastic total occlusion at the left main tract in a single coronary artery.

A 64-year-old man was admitted to hospital under the suspicion of unstable angina pectoris. Coronary angiography showed that he has a single coronary artery originating from the right coronary artery (RCA) without significant fixed stenosis. Acetylcholine was superselectively infused into the left main coronary artery (LMCA), and confirmed the coronary vasospastic occlusion associated with chest pain and elevation of the ST-segment in the precordial leads. This is the first report of the induction of a totally occlusive spasm of the LMCA of a patient with a RCA type single coronary artery, and this case suggests that spasm of the aberrant coronary artery is a potential mechanism for sudden death in patients with a single coronary artery.

Angina Pectoris, Variant↗

PubMed2001

Characteristics of learning and memory impairment induced by delta9-tetrahydrocannabinol in rats.

We investigated the characteristics of delta9-tetrahydrocannabinol (THC)-induced impairment of learning and memory using an 8-arm radial maze task, a water maze, a visual discrimination task with 2 figures and a passive avoidance test in rats. THC (6 mg/kg, i.p.) impaired spatial memory in the standard task of the 8-arm radial maze. THC (4-6 mg/kg, i.p.) selectively impaired working memory in a reference and working memory task of the 8-arm radial maze. Even at a dose of 10 mg/kg, THC did not impair spatial memory in the water maze. In addition, THC at a dose of 6 mg/kg, which had inhibitory effects in the 8-arm radial maze, did not affect performance in the visual discrimination task. These results indicate that at low doses (2-6 mg/kg), THC may not produce visual function abnormalities. THC impaired retrieval (6 mg/kg, i.p.) as well as acquisition (10 mg/kg, i.p.) in the passive avoidance test. The consolidation process was also impaired by i.c.v. injection (100 microg), but not i.p. injection (6-10 mg/kg) of THC. These results suggest that THC-induced impairment of spatial memory is based on the selective impairment of working memory through its effects on acquisition and retrieval processes.

Animals↗

PubMed2001

Primary culture of chicken hepatocytes as an in vitro model for determining the influence of dioxin.

An easy method for primary culture of chicken hepatocytes was developed to study the influence of dioxin on birds. Chicken hepatocytes could maintain gene expression and protein secretion of albumin for a long period in serum-free medium with free atmosphere exchange at 37 degrees C. Moreover, the cells showed a sensitive response to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) by monitoring the expression of P450 1A, theta GST (theta-GST) and albumin genes.

Albumins↗

PubMed2001

Determination of anti-virus drug, ganciclovir, in human serum by HPLC with precolumn fluorescence derivatization using phenylglyoxal.

A selective and highly sensitive liquid chromatographic method for the determination of ganciclovir (anti-virus drug) in human serum was described. After ganciclovir and acyclovir (internal standard; IS) were extracted with solid-phase extraction cartridge from serum, they were converted into fluorescent derivatives by reaction with phenylglyoxal in a phosphate buffer (pH 5.8) at 20 degrees C for 30 min. The derivatives were separated by reversed-phase column with a mixture of acetonitrile-1 mM phosphate buffer (pH 6.2) (18:82, v/v), and were then detected spectrofluorometrically at 512 nm with excitation at 365 nm. Extraction recoveries were 87.0-91.6% for ganciclovir and 86.8-92.3% for IS. The detection limit for ganciclovir spiked to serum was 5 ng ml-1 serum (306 fmol on column) at a signal-to-noise ratio of three. The accuracy and precision of this method were 7.6% and 5.0% even at low concentration (20 ng ml-1). The within- and between-day variations are lower than 7.6% and 8.1%, respectively.

Acyclovir↗