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Biomedical subjects

M Asai

Publications and source records attributed to M Asai.

At least 55 records · Page 3Linked to original sources
PubMed2000

N-methyl-D-aspartate receptor subtype 2C is not involved in circadian oscillation or photoic entrainment of the biological clock in mice.

Ishida et al. [1994: Neurosci Lett 166: 211-215] reported the circadian change of N-methyl-D-aspartate (NMDA) receptor subtype 2C mRNA and photic induction of this receptor's mRNA in the suprachiasmatic nucleus (SCN). Therefore, we investigated the role of NMDA receptor subtypes in the biological clock using NMDA receptor 2A (NR2A)- or 2C (NR2C)-deficient mice. However, NR2C-/- mice showed normal light-dark (LD)-entrained locomotor activity rhythms and free-running rhythms under constant darkness and also exhibited normal reentrainment to 6-hr LD shifts and phase delays with single light pulses. Thus, present results demonstrated no significant NR2C contribution to circadian oscillation and photic entrainment, even though expression of NR2C mRNA was highly observed in the SCN. On the other hand, the period of the free-running activity rhythm in NR2A-/- mice but not NR2C-/- mice was slightly longer than that in wild-type mice in spite of low expression of NR2A in the SCN. Furthermore, reentrainment to an LD advance in NR2A-/- mice was slower under low-intensity light conditions. Thus, we suggest that NR2A plays a role in determining the behavioral state that affects the circadian rhythm. In order to elucidate the role of NR2A and NR2C in the SCN, we examined NMDA-induced Ca(2+) elevations in the SCN of mutant mice using a Ca(2+) imaging method. A partial reduction in Ca(2+) elevation was observed in both NR2A-/- and NR2C-/- mice when high concentrations (100 or 300 microM) of NMDA were applied. The present results suggest that NR2A plays a weak role in oscillation or entrainment of the biological clock, and that NR2C does not participate in the functions of circadian oscillation and light entrainment.

Animals↗
PubMed2000

Administration of melatonin in drinking water promotes the phase advance of light-dark cycle in senescence-accelerated mice, SAMR1 but not SAMP8.

We analyzed effects of aging on behavioral rhythms in the mouse showing senescence acceleration, SAMP8 strains. The free-running rhythms had longer free-running periods (tau) in SAMP8 than in the control strain (SAMR1). Drinking of melatonin promoted the adaptation to advanced LD in SAMR1 but not in SAMP8, although both strains exhibited melatonin MT1 and MT2 receptors. The present results suggest that melatonin promotes the adaptation to advanced LD cycles in normal aging mice.

Adaptation, Physiological↗
PubMed2000

Core-excited states in the doubly magic 68Ni and its neighbor 69Cu

In deep-inelastic collisions of 8 MeV/nucleon 70Zn projectiles with 198Pt, we have found an 8(+) isomer with T(1/2) = 23(1) ns at 4208 keV in 68Ni; the nug(9/2) E2 effective charge was determined to be 1. 5(1)e. In 69Cu, a 19/2(-) isomer with T(1/2) = 22(1) ns at 3691 keV was identified and its decay data were calculated quite accurately by a parameter-free shell model calculation using empirical input parameters. Proton 2p- 1h excitation, fed by another T(1/2) = 39(6) ns isomer at 3827 keV, induces large collectivity in 69Cu.

Journal Article↗
PubMed2000

Potato micro-tuber inducing hydroxylasiodiplodins from Lasiodiplodia theobromae.

Three hydroxylasiodiplodins were isolated from the mycelium extracts of Lasiodiplodia theobromae IFO 31059; and their structures were identified as (3R),(4S)-4-hydroxylasiodiplodin, (3R),(6R)-6-hydroxy-de-O-methyllasiodiplodin and (3R),(5R)-5-hydroxy-de-O-methyllasiodiplodin. All showed potato micro-tuber inducing activity.

Heterocyclic Compounds, 2-Ring↗
PubMed2000

Urinary pyrimidine analysis in healthy newborns, infants, children, adults and patients with congenital metabolic diseases.

BACKGROUND: In previous reports, the reference range for urinary pyrimidine was determined on the basis of a small number of samples, with data for only a few patients being reported. In the present study, we measured urinary pyrimidine compounds in 25 healthy newborns, 33 healthy infants, 130 healthy children and 166 healthy adults. In addition, we also analyzed urinary pyrimidine compounds in various patients with abnormal pyrimidine metabolism, such as congenital pyrimidine metabolism disorders and urea cycle disorders. METHODS: We analyzed urines by high-performance liquid chromatography with column switching. Analyses were performed with both a reverse-phase column and an anion-exchange column. The columns were connected by a column switch, with all systems being controlled automatically by a computerized system controller. RESULTS: The excretion of pyrimidine compounds in patients with abnormal pyrimidine metabolism (containing heterozygotes) was out of our reference ranges. CONCLUSIONS: These results suggest that urinary pyrimidine analysis is a useful index for the diagnosis of pyrimidine metabolism disorders, urea cycle disorders and these heterozygotes. Based on this large-group analysis of healthy individuals, we were able to determine the reference ranges of urinary orotic acid, dihydrouracil and uracil for each age group.

Adolescent↗
PubMed2000

Postoperative complications and functional results after total glossectomy with microvascular reconstruction.

Microsurgical reconstruction after total glossectomy can greatly improve quality of life; however, postoperative functional results are often unstable, and the effectiveness of total glossectomy remains questionable. To determine the problems of reconstruction after total glossectomy with laryngeal preservation and to examine the functional results of swallowing and speech, 30 patients who had undergone total glossectomy and reconstruction with free flaps were reviewed for this study. The patients ranged in age from 20 to 73 years, and 23 of the 30 had undergone reconstruction with a rectus abdominis musculocutaneous flap. Wider and thicker flaps were designed and transferred and were sutured to suspend the larynx. To maintain physiologic swallowing function after surgery, the extent of laryngeal suspension and cricopharyngeal myotomy was limited. Of the 30 patients, 21 (70 percent) could be decannulated with laryngeal preservation; 20 of these 21 could tolerate a normal/soft/pureed diet, and 1 was limited to a fluid diet. Speech was intelligible in 16 of the 19 patients evaluated. In 9 of the 30 patients, laryngeal function could not be preserved. In four of these nine patients, additional resection combined with total glossectomy caused severe aspiration and recurrent pneumonia. Two patients with preoperative cerebral dysfunction were also poor candidates for laryngeal preservation. Additionally, the transferred flap's lack of bulk in the oral cavity and the advanced age (73 years) of one patient and the poor motivation of another may have contributed to postoperative aspiration. Aspiration occurred in one patient because of local recurrence of a tumor. The presence of preoperative cerebral dysfunction (p = 0.025), resection of the epiglottis (p = 0.005), and postoperative orocutaneous fistulas (p = 0.04) were significantly associated with the failure of laryngeal preservation. However, because of the difficulty of enrolling a sufficient number of patients in the study and the inherent limitations of retrospective studies, multivariate analysis in this study showed that no factors, such as patient age, flap volume, and the type of neck dissection, were significant predictors of laryngeal preservation. Although prospective studies are necessary, the function of individual patients must be assessed so that the study experiences discussed here can be applied to subsequent patients.

Adult↗
PubMed2000

Antidiabetic sulfonylurea enhances secretagogue-induced adrenocorticotropin secretion and proopiomelanocortin gene expression in vitro.

The presence of high-affinity binding sites for antidiabetic sulfonylureas (SUs) and the expression of SU receptor (SUR) messenger RNA in the adenohypophyseal cells have recently been reported. In this study, we examined the effects of SU on POMC gene expression and ACTH secretion using the AtT20PL cell line, a subclone of AtT20 in which the rat POMC 5'-promoter-luciferase fusion gene was stably incorporated. A representative SU glibenclamide inhibited the basal POMC 5'-promoter activity. In contrast, glibenclamide enhanced forskolin- or CRH-induced POMC expression in a dose-dependent manner. Interestingly, the latter effect was not observed under treatment with 3-isobutyl-1-methylxanthine, a nonselective phosphodiesterase inhibitor. Furthermore, diazoxide, an opener of the ATP-sensitive K+ channel, only antagonized the suppressive effect of glibenclamide. Lastly, RT-PCR analysis showed that mouse SUR (but not SUR2) messenger RNA was expressed in this cell line. These results suggest that, in AtT20PL cells, SU has dual effects, i.e. a suppressive effect on basal POMC expression through diazoxide-sensitive (ATP-sensitive) K+-channel-mediated mechanism, and an enhancing effect on cAMP/protein kinase A-stimulated POMC expression through a different mechanism (probably mediated by phosphodiesterase). To our knowledge, this is the first report showing the effect of SU on the expression of the anterior pituitary hormone gene.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Genetic structure of the five-factor model of personality in a Japanese twin population.

Dimensional approaches have been used to describe the fundamental dimensions that underlie the entire domain of normal and pathological personality. We tested the five factor model of personality structure in a sample of Japanese twins, to clarify the contributions of genetic and environment. The revised NEO personality inventory (NEO-PI-R) was administered to 251 twin pairs, ranging in age from 15 to 27 years of age. The NEO-PI-R is a 240-item questionnaire which was developed to assess the dimensions of personality. Univariate genetic analysis showed that the AE model in which phenotypic covariances are explained only by additive genetic (A) and nonshared environment (E) is still a plausible model, and that the relative proportion of genetic influence was comparable to that reported by Loehlin (1992). Multivariate genetic analysis of the Japanese data suggested/revealed that the five factors are genetically dependent on each other and one common genetic factor mediates their interdependence. Previous studies have assumed that they are phenotypically independent and robust. Although there are sampling biases in the present study, it is noteworthy that the results for all five factors depicted by the NEO-PI-R were comparable to those reported by Western researchers, and the genetic structure of the five-factor model is complex.

Adolescent↗
PubMed2000

[Improvement in quality of life with vinorelbine as a single agent in two patients with recurrent lung cancer].

Two patients with lung cancer that recurred after surgery and chemotherapy were administered vinorelbine (20 mg/m2) as a single agent on days 1 and 8 every 4 weeks. Patient 1 had recurrences in both lung lobes and metastases in the bone and liver after surgery, while patient 2 had a recurrence in the left lung lobe and metastases in the brain and liver after prior chemotherapy. In both patients, vinorelbine treatment improved several clinical indicators of cancer symptomatology including serum LDH, levels of other clinical blood tests, as well as a subjective assessment of the quality of life (QOL). Both patients were discharged from the hospital and subsequently treated on an outpatient basis. Because recurrent lung cancer patients generally have a poor performance status, chemotherapy for these patients is thought to worsen the QOL and increase hospital stays. The present report suggests that vinorelbine, as a single agent, might improve the QOL and make it possible to treat recurrent lung cancer patients on an outpatient basis.

Adenocarcinoma↗
PubMed2000

Involvement of caveolin-1 in cholesterol enrichment of high density lipoprotein during its assembly by apolipoprotein and THP-1 cells.

High density lipoprotein (HDL) is assembled by interaction of apolipoprotein A-I with human monocytic leukemia cell line THP-1 by removing cellular cholesterol and phospholipid. Although the HDL formed with undifferentiated THP-1 cells contained only phosphatidylcholine and almost no cholesterol, the cells differentiated with phorbol 12-myristate 13-acetate (PMA) generated HDL enriched in cholesterol. The extent of cholesterol enrichment related to the cellular cholesterol level in the differentiated cells, but only weakly in the undifferentiated cells. In contrast, the differentiation had no influence on the diffusion-mediated cellular cholesterol efflux. The undifferentiated cells expressed the messages of ATP-binding cassette transporter 1 and caveolin-1, at low levels, and the PMA-induced differentiation resulted in substantial expression of both messages. Caveolin-1 protein expression was also highly induced by the PMA treatment of THP-1 cells. When the cells were treated with the antisense DNA of caveolin-1 and differentiated, both caveolin-1 synthesis and cholesterol incorporation into the HDL were reduced in parallel to generate the cholesterol-poor HDL. We concluded that caveolin-1 is involved in enrichment with cholesterol of the HDL generated by the apolipoprotein-cell interaction. This function is independent of the assembly of HDL particles with cellular phospholipid and of nonspecific, diffusion-mediated efflux of cellular cholesterol.

Apolipoprotein A-I↗
PubMed1999

Stereocontrolled Synthesis of (-)-5,11-Dideoxytetrodotoxin.

New derivatives of an intriguing marine natural product are now accessible. The first asymmetric synthesis of the simple tetrodotoxin analogue, 5,11-dideoxytetrodotoxin (3), was achieved. Hydroxylation at position C8 of the key intermediate 1 relied on the neighboring trichloroacetamide group, and stereoselective elaboration of the vinyl group gave alpha-hydroxylactone 2, which was transformed into the title compound through a new guanidylation method.

Journal Article↗
PubMed1999

Biological and biochemical properties of Ret with kinase domain mutations identified in multiple endocrine neoplasia type 2B and familial medullary thyroid carcinoma.

Several mutations were identified in the kinase domain of the RET proto-oncogene in patients with multiple endocrine neoplasia (MEN) 2B, familial medullary thyroid carcinoma (FMTC) or sporadic medullary thyroid carcinoma. We introduced seven mutations (glutamic acid 768-->aspartic acid (E768D), valine 804-->leucine (V804L), alanine 883-->phenylalanine (A883F), serine 891-->alanine (S891A), methionine 918-->threonine (M918T), alanine 919-->proline (A919P) and E768D/A919P) into the short and long isoforms of RET cDNA and transfected the mutant cDNAs into NIH3T3 cells. The transforming activity of the long isoform of Ret with each mutation was much higher that that of its short isoform. Based on the levels of the transforming activity, these mutant RET genes were classified into two groups; a group with high transforming activity (A883F, M918T and E768D/A919P) and a group with low transforming activity (E768D, V804L, S891A and A919P) (designated high group and low group). Interestingly, the level of transforming activity correlated with clinical phenotypes; high group Ret with the A883F or M918T mutation and low group Ret with the E768D, V804L or S891A mutation were associated with the development of MEN 2B and FMTC, respectively. In addition, we found that substitution of phenylalanine for tyrosine 905 present in the kinase domain abolished both transforming and autophosphorylation activities of low group Ret whereas it did not affect the activities of high group Ret.

Amino Acid Substitution↗
PubMed1999

Biochemical markers of bone turnover during hormone replacement therapy.

OBJECTIVE: To assess the clinical usefulness of bone turnover markers, including serum osteocalcin (OC), urinary pyridinoline (Pyr) and deoxypyridinoline (D-Pyr), in monitoring and predicting bone response to hormone replacement therapy (HRT). METHOD: The relationships between baseline levels or changes in markers and change in lumbar bone mineral density were examined in 21 surgically-induced postmenopausal women. RESULTS: Levels of OC, Pyr and D-Pyr in the estrogen effective group (responders) significantly decreased during HRT and baseline levels of Pyr and D-Pyr in responders were significantly higher than those in premenopausal women. CONCLUSION: Bone turnover markers were useful in monitoring the bone effect of HRT and baseline levels of markers reflect subsequent bone response to HRT.

Amino Acids↗
PubMed1999

Estimation of intradermal disposition kinetics of drugs: I. Analysis by compartment model with contralateral tissues.

PURPOSE: The objectives of dermal application of drugs are not only systemic therapeutic, but also local ones. We would expect its intradermal kinetics to be dependent on its therapeutic purpose. To develop more efficient drugs for local or systemic therapeutics, it will be important to estimate quantitatively the intradermal disposition of drugs applied topically. We tried, therefore, to develop the compartment model to describe the intradermal disposition kinetics after topical application of drugs. METHODS: In vivo percutaneous absorption study for antipyrine, a model compound, was performed using rats with tape-stripped skin, using the assumption that the stratum corneum permeability to drugs would be improved enough not to be a rate-limiting process. RESULTS: To analyze the results obtained, a 4-compartment model, composed of donor cell, viable skin, muscle, and plasma compartments, was applied. Although the fitting lines obtained could describe the concentration-time profiles of antipyrine in each compartment very well, the concentration profiles in the contralateral tissues were extensively overestimated. Therefore, we developed a 6-compartment model which included the viable skin and muscle in the contralateral site, and analysed the concentration-time curve of each compartment. The fitting curves were in good agreement with the experimental data for all the compartments including the contralateral viable skin and muscle, and thus, this model was recognized to be adequate for the estimation of intradermal kinetics after topical application. Judging from the obtained values of clearance from viable skin to plasma and from viable skin to muscle, about 80% of antipyrine penetrated into viable skin, which suggested it was absorbed into circulating blood and 20% was transported to muscle under viable skin. CONCLUSIONS: Pharmacokinetic analysis using the 6-compartment model would be very useful for the estimation of local and systemic availability after topical application of drugs.

Administration, Topical↗
PubMed1999

Differential generation of high-density lipoprotein by endogenous and exogenous apolipoproteins in cultured fetal rat astrocytes.

Most peripheral cells generate cholesterol-rich high-density lipoprotein (HDL) with exogenous apolipoprotein as one of the mechanisms for the maintenance of cellular cholesterol homeostasis. Astrocytes isolated from fetal rat brain showed a unique behavior in this reaction. Consistent with previous findings, the astrocytes synthesized apolipoprotein (apo) E and generated cholesterol-rich pre-beta-HDL-like lipoprotein with this apoE, and cellular cholesterol and phospholipids. When exogenous apoA-I and E were added to the medium, they caused generation of additional HDL with cellular phospholipid. It is interesting that this additional part was very poor in cholesterol except for the generation of relatively cholesterol-rich HDL only in the initial few hours of the incubation. The mobilization of intracellular cholesterol for this reaction was also very limited, reflecting the poor cholesterol incorporation into the HDL. Thus, the results demonstrated a unique profile of HDL generation and cholesterol efflux by apolipoproteins in rat astrocytes, with endogenous apoE producing cholesterol-rich HDL and exogenous apolipoproteins producing cholesterol-poor HDL. These lipoproteins may play differential roles in cholesterol transport in the CNS.

Animals↗
PubMed1999

Evaluation of a cement incus replacement prosthesis in a temporal bone model.

In reconstruction of the ossicular chain for a damaged incus, it is important that the incus replacement prosthesis (IRP) length is ideal in order to provide optimal tension between the tympanic membrane or malleus and stapes head to achieve the best post-operative hearing result. Even though the length of commercially available IRPs can be adjusted, it still may be difficult to achieve clinically. We describe experiments in a human temporal bone model using dental cement as an IRP after removal of the incus. This cement IRP (CIRP) hardens in situ and becomes the length of the gap to be spanned so that tension should be ideal. Two different CIRPs were studied; one was a conventional rod-type CIRP connecting either the umbo or mid-malleus handle to the stapes head. The second was a Y-shaped CIRP (Y-CIRP), connecting two sites on the malleus to the stapes head. The wide Y-CIRP connected the malleus head and umbo to the stapes head, while the narrow Y-CIRP connected the malleus neck and mid-handle to the stapes head. The acoustic performance of these experimental CIRPs was studied using a laser Doppler vibrometer system in 12 fresh human temporal bones. The CIRP demonstrated better acoustic performance than conventional IRPs studied previously in the same model. While all the CIRPs showed similar function below 2.0 kHz, the narrow Y-CIRP appeared best above 3.0 kHz. A prosthesis of this type may have an acoustic advantage over conventional IRPs.

Acoustic Stimulation↗
PubMed1999

Analysis of the best site on the stapes footplate for ossicular chain reconstruction.

Experiments were performed in 22 fresh human temporal bones to compare the relative acoustic function of three stapes footplate sites for an incus stapes superstructure replacement prosthesis (I-SRP). The three sites evaluated were the anterior, centre and posterior footplates. A new round window (RW) measurement method was used to make the comparisons. A small glass microsphere was placed in the centre of the RW as a target. A Polytec laser Doppler vibrometer was used to measure round window displacement in response to 50 pure tones between 200 and 10,000 Hz presented at 80 dB SPL at the tympanic membrane (TM). After a baseline measurement of RW displacement in the intact temporal bone, the incus was removed and a cement I-SRP (CIRP) formed between the mid-malleus handle and each of the three test footplate sites, in random order. RW displacement was again measured after placement of the CIRP at each of three sites. We found the centre site to be 3.0-7.0 dB better than the anterior site above 2,000 Hz. There were no differences between the anterior and centre sites below 2,000 Hz. The posterior site was the worst at all frequencies.

Aged↗