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Biomedical subjects

Y Takeuchi

Publications and source records attributed to Y Takeuchi.

At least 289 records · Page 16Linked to original sources
PubMed1998

T-cell receptor variable gene analysis of renal allograft-infiltrating cells in biopsy specimens using a nonradioisotopic micromethod.

BACKGROUND: A sensitive micromethod for T-cell receptor (TCR) analysis is needed for clonality analysis of renal allograft-infiltrating T cells (RAITs) obtained by needle biopsy. METHODS: TCR cDNA was amplified by the anchored polymerase chain reaction and was hybridized with 28 different TCR beta variable (TCRBV) genes fixed on nylon membranes, and the percentage of each TCRBV gene was measured spectrophotometrically. RESULTS: The specificity and linearity of the hybridization technique and the constancy of the TCRBV percentages over a wide range of sample amounts were demonstrated by control experiments. Analysis of RAITs of biopsy specimens from four patients showed broad or skewed TCRBV usage, indicating the presence of polyclonal and oligoclonal RAIT populations, respectively. In one patient who received OKT3 immunosuppressive treatment, the TCRBV skewness was dramatically reduced after the treatment. CONCLUSION: We have established a powerful method for analyzing RAIT clonality, which is especially useful for monitoring RAIT dynamics after immunosuppression therapy.

Acute Disease↗
PubMed1998

Influence of Surfactant Structure on the Drainage of Nonionic Surfactant Foam Films.

The stability of vertical liquid films produced from aqueous solutions of polyoxyethylene alkyl ether (CnEm) was studied by monitoring the dynamic surface tension (gammat) and aqueous core thickness of a vertical foam film (d2) measured by FT-IR. The temperature dependence of the drainage patterns of the liquid films was clarified for CnE8 (n = 10, 12, 14, and 16) solutions. It was found that the critical thickness (Drup) where the film rupture happens increased with increasing temperature in the case of C10E8 and C12E8, while Drup remarkably decreased and finally formed a black film in the case of C14E8 and C16E8 solutions within the measured temperature range. In addition, a delay in the film drainage occurred in these systems, which was caused by the stabilization of the films via the Marangoni effect proved by dynamic surface tension measurements. On the other hand, heterogeneous ethoxylated dodecyl ethers (C12Em) modified with a hydrophilic group showed a remarkable increment of Drup under dynamic conditions without the Marangoni stabilization in the foam film. Adding a hydrophobic group at the end of the polar head produces a large area per molecule and causes a large increase in the surface coverage of the air bubbles. However, a less structured surface coverage facilitated the breaking of the foam during the Ross and Miles test. These results indicate that under dynamic conditions, the Marangoni effect and the hydrophobic interaction at the surface become important for foam film rupture. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Derivation of a three-dimensional pharmacophore model of substance P antagonists bound to the neurokinin-1 receptor.

Constrained systematic search was used in an exhaustive conformational analysis of a structurally diverse set of substance P (SP) antagonists to identify a unique hypothesis for their bound conformation at the neurokinin-1 receptor. In this conformation, two aromatic groups essential for high affinity adopt a perpendicular or edge-on arrangement. This pharmacophore hypothesis for the receptor-bound conformation was used in a comparative molecular field analysis (CoMFA) of an expanded set of SP antagonists, and the predictive ability of the resulting three-dimensional quantitative structure-activity relationship (3D-QSAR) was evaluated against a test set of SP antagonists different from those in the training set. This CoMFA model based on the Constrained Search alignment yielded significant cross-validated, conventional, and predictive r2 values equal to 0.70, 0.93, and 0.82, respectively. For comparison, the SP antagonists were forced into an alternative poorer alignment in which the two aromatic rings were parallel and then subjected to a CoMFA analysis. Both the parallel and perpendicular arrangements of the aromatic rings are seen in X-ray structures of SP antagonists and have been proposed as candidates for the receptor-bound conformation. The parallel (or stacked) conformation yielded a poorer correlation with a cross-validated r2 = 0.57, a conventional r2 = 0.90, and a predictive r2 = 0.78. Our results indicate that although both alignments could generate a reasonable CoMFA correlation, the stacked conformation is unlikely to be the receptor-bound conformation, as the covalent structure of the antagonists precludes a common geometry in which the aromatic rings are stacked.

Binding Sites↗
PubMed1998

No evidence of pig DNA or retroviral infection in patients with short-term extracorporeal connection to pig kidneys.

BACKGROUND: The xenotransplantation of organs and tissues, in particular those from pigs, is viewed as a means to alleviate the shortage of human donor organs and cells available for transplantation and also as a therapy for other diseases. The potential microbiological hazards of xenotransplantation have recently attracted much attention. One concern is over pig endogenous retroviruses (PERV). Until the possible consequences of infection by PERV are better understood it is unlikely that a significant number of porcine xenotransplants will proceed. However, a small number of patients have already been treated with or exposed to living porcine cells or tissue, and investigation of these patients may provide valuable information. METHODS: We took serial blood samples from two renal dialysis patients whose circulation had been linked extracorporeally to pig kidneys and tested them for pig DNA and PERV DNA by nested PCR. The patients' plasma was also tested for neutralising antibodies to two anthropotropic PERV strains. FINDINGS: Having established that the nested PCRs could detect single molecules of target sequence, we analysed DNA isolated from patients' peripheral blood mononuclear cells. We found no evidence of pig or PERV DNA in either patient, even in samples taken as early as 6 h after the perfusion. Furthermore, we found no evidence of seroconversion for PERV-specific antibodies. INTERPRETATION: The absence of porcine cells in the circulation of both patients, even in the samples taken soon after the perfusion experiment, suggests that any porcine cells dislodged from the kidney became rapidly sequestered from the circulation. Since cell-to-cell contact increases the efficiency of infection of PERV this removal of porcine cells may increase the risk of transmission of PERV to the xenograft recipient. We did not, however, detect indications of infection by PERV by PCR or neutralisation assay. The genetic and serological methods described here will be useful for detection of possible PERV infection in other patients.

Adult↗
PubMed1998

Anti-AIDS agents. 33. Synthesis and anti-HIV activity of mono-methyl substituted 3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK) analogues.

Four isomeric methyl substituted DCK analogues (2-5) were asymmetrically synthesized from different starting materials. 3-Methyl, 4-methyl, and 5-methyl-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (2-4) all were extremely potent against HIV-1 replication in H9 lymphocyte cells with EC50 and therapeutic index values of < 4.23 x 10(-7) microM and > 3.72 x 10(8), respectively, which are much better than those of DCK and AZT in this assay.

Anti-HIV Agents↗
PubMed1998

Identification of major wheat allergens by means of the Escherichia coli expression system.

Wheat proteins were fractionated into salt-soluble, glutenin-rich, and gliadin-rich fractions. Reactivities of these protein fractions with sera of patients with wheat-associated allergies were examined under various conditions. The relative reactivity of the fractions was generally in the order glutenin-rich > gliadin-rich >> salt-soluble fractions, although their reactivities were variable among patients and among the reaction conditions, indicating that the kind, the number and the epitope of allergens were variable among patients. To identify major allergens, alpha-, gamma- and omega-gliadin, and low-molecular-mass (LMM)- and high-molecular-mass (HMM)-glutenin genes were expressed in Escherichia coli by means of a pET vector. Recombinant gliadins and glutenins were partially purified on the basis of the solubilities of prolamin and glutelin. The partially purified recombinant proteins were reacted with the patients' sera. LMM glutenin containing many Gln-Gln-Gln-Pro-Pro motifs, which was identified to be IgE-binding epitope [Tanabe, S., Arai, S., Yanagihara, Y., Mita, H., Takahashi, K. & Watanabe, M. (1996) Biochem. Biophys. Res. Commun. 219, 290-293], exhibited the highest reactivity. The next highest reactivities were observed on alpha-gliadin and gamma-gliadin, which had not been identified as allergens.

Adult↗
PubMed1998

Rational design of antitumor prostaglandins with high biological stability.

microolecular design can overcome the metabolic instability of Delta7-PGA1, while maintaining its antitumor potency. Saturation of the C(13)-C(14) double bond enhances the biological stability but decreases the antiproliferative activity. Configurational inversion of the isomerase-sensitive C(12) stereocenter from the natural S to the unnatural R geometry not only enhances biological stability but also significantly suppresses the growth of the tumor cells. The 12R derivatives markedly increase the induction of p21, a Cdk inhibitor, leading to sharp cell cycle arrest at the G1 phase at a dose level so low that at this dose Delta7-PGA1 methyl ester scarcely exerts an effect. These conspicuous biological properties lead to long-term suppression of tumor cell growth. The structure-stability relationship demonstrates that the stability of prostaglandins (PGs) is crucially controlled by the C(12) configuration and is unaffected by the geometry of the hydroxy-bearing C(15). The successful design of antitumor PGs resistant to enzymatic metabolism provides a new strategy applicable to creating a useful PG for cancer chemotherapy.

Animals↗
PubMed1998

Effects of age and ethanol on dopamine and serotonin release in the rat nucleus accumbens.

Neural functions in the nucleus accumbens (ACC) play an important role in alcohol drinking behavior. In the present study, we observed the effects of age and ethanol (EtOH) on dopamine (DA) and serotonin (5-HT) release in the ACC of freely moving 4-, 10-, and 16-month-old rats using brain microdialysis techniques. After co-perfusion with 200 mM ethanol, ACC DA, and 5-HT release were decreased significantly in 16-month-old rats compared to those at 4 months old. ACC DA and 5-HT neurons of aged rats were less sensitive to ethanol. On the other hand, both basal extracellular DA and 5-HT release in the ACC were significantly higher in 16-month-old than in 4-month-old rats. Therefore, aging results in opposite changes in basal and alcohol-induced DA and 5-HT release in the ACC.

Aging↗
PubMed1998

Retroviral vector targeting to melanoma cells by single-chain antibody incorporation in envelope.

Two strategies for targeting recombinant retroviruses to melanoma cells were compared. One was to extend the tropism of an ecotropic envelope to human melanoma cells, the other was to enhance the tropism of an amphotropic envelope for melanoma cells. Chimeric retroviral envelopes, incorporating a single-chain antibody (ScFv) directed against high-molecular-weight melanoma-associated antigen (HMWMAA) at the amino terminus are correctly processed and incorporated into virions. ScFv-ecotropic envelope chimeras allow specific, but low-titer, targeting of HMWMAA-positive cells, when co-expressed with ecotropic envelopes. ScFv-amphotropic envelope chimeras bind specifically to HMWMAA-positive cells and allow preferential infection at high titer.

Amino Acid Sequence↗
PubMed1998

Characterization of a 34-kDa soybean binding protein for the syringolide elicitors.

Syringolides are water-soluble, low-molecular-weight elicitors that trigger defense responses in soybean cultivars carrying the Rpg4 disease-resistance gene but not in rpg4 cultivars. 125I-syringolide 1 previously was shown to bind to a soluble protein(s) in extracts from soybean leaves. A 34-kDa protein that accounted for 125I-syringolide 1 binding activity was isolated with a syringolide affinity-gel column. Partial sequences of internal peptides of the 34-kDa protein were identical to P34, a previously described soybean seed allergen. In soybean seeds, P34 is processed from a 46-kDa precursor protein and was shown to have homology with thiol proteases. P34 is a moderately abundant protein in soybean seeds and cotyledons but its level in leaves is low. cDNAs encoding 46-, 34-, and 32-kDa forms of the soybean protein were cloned into the baculovirus vector, pVL1392, and expressed in insect cells. The resulting 32- and 34-kDa proteins, but not the 46-kDa protein, exhibited ligand-specific 125I-syringolide binding activity. These results suggest that P34 may be the receptor that mediates syringolide signaling.

Allergens↗
PubMed1998

Effect of maternal deprivation on N-acetyltransferase activity rhythm in blinded rat pups.

It has been reported that the rhythms of infant rats synchronize with the mother's rhythm until the light-dark cycle comes and has strong effects on their endogenous clocks. We found that periodic maternal deprivation (PMD) was able to cause a phase shift of serotonin N-acetyltransferase (NAT) in neonatal blinded rat pups. PMD in which contact with the mother was allowed for only 4 h caused a phase shift of NAT rhythm, irrespective of the timing of contact with the mother in a day. Acute single mother deprivation caused an excess of NAT activity for more hours than usual and contact with the mother prevented such an excessive response. Mother deprivation may act as a cold stress, since artificial warming of pups gave the same results as contact with the mother. When the pups were artificially warmed by a heater during a 1-week deprivation period, a flat 24-h pattern of NAT was observed. The mechanism causing a phase shift of NAT activity rhythm of rat pups may be complicated.

Animals↗
PubMed1998

Mode of migration of normal lymphocytes inside murine testis.

BACKGROUND: Previous studies have shown that in murine experimental autoimmune orchitis (EAO), lymphocytes preferably infiltrate into (1) the testicular capsule near the rete testis, (2) the subcapsular interstitium away from the rete testis, and (3) the interstitium surrounding the tubuli recti and rete testis. Therefore, these three sites might provide tissue environments in which specific lymphocytes can easily gain access to testicular autoantigens. However, there is another possibility that infiltrating lymphocytes in the testis spontaneously accumulate at these three sites via the lymphatic flow inside this organ during EAO. METHODS: To examine this possibility, normal lymphocytes were locally injected into the peripheral testis regions of recipient mice. Testes were then collected at various times for investigating the chronological pattern of lymphocytic migration inside the testes at a light microscopic level. RESULTS: The injected lymphocytes first stayed in the lymphatic space around the seminiferous tubules and then moved to the subcapsular lymphatic space away from the rete testis. The lymphocytes accumulated under the testicular capsule and then gradually infiltrated into the adjacent capsular tissue. In the capsule, the cells surrounded the arteriolae and then accumulated in the capsular tissue near the rete testis. Thereafter, the cells finally left the testes through the lymphatics running in the spermatic cords. In the course of the lymphocytic drainage, it was noted that the injected lymphocytes appeared not to pass through the testicular interstitium around the tubuli recti and rete testis. CONCLUSIONS: The regional distributions of the testicular lymphocytes imply that the lymphatic flow in the testis may somewhat influence murine EAO pathology characterized by lymphocytic accumulation in (1) the testicular capsule near the rete testis and (2) the subcapsular interstitium away from the rete testis. However, the pathology exhibiting lymphocytic accumulation in (3) the interstitium around the tubuli recti and rete testis is independent on the intratesticular lymph flow.

Animals↗
PubMed1998

[Efficacy and safety of a single oral dose of pilsicainide in supraventricular arrhythmia after coronary artery bypass grafting].

We evaluated the efficacy and safety of administration of a single oral dose of Pilsicainide, a class Ic antiarrhythmic agent, in 34 patients (26 men, 8 women, age from 48 to 81, mean age 66 +/- 8 years) who developed supraventricular arrhythmia after coronary artery bypass grafting (CABG). A total of 42 episodes of postoperative supraventricular arrhythmia, with the majority occurring 2-4 days after CABG, were classified as follows: paroxysmal atrial fibrillation, 34; paroxysmal atrial flutter, 6; and sinus tachycardia, 2. Sinus rhythm was restored in 32 episodes (78%) by treatment with oral pilsicainide given in a single dose of 50 ro 100 mg. Successful conversion was obtained within 90 minutes in 44% and 3 hours in 56% of episodes, with a mean conversion time of 119.2 +/- 107.5 minutes after the administration of pilsicainide. The mean conversion times tended t highlight the difference between the 50 mg and 100 mg doses, but this difference was not statistically significant (p = 0.053). The ventricular rate was significantly reduced from 123.3 +/- 29.5 beats/min to 85.6 +/- 19.9 beats/min (p < 0.0001), however no significant changes in blood pressure or no significant side effects were observed. The results of the present study suggest that a single oral dose of pilsicainide, administered for its favorable pharmacokinetic profile and lack of hemodynamic side effects, is a valuable drug for converting supraventricular arrhythmia to sinus rhythm in most patients after CABG.

Aged↗
PubMed1998

[Hemodynamic evaluations of patients with small aortic annulus with St. Jude Medical prosthetic heart valve].

As the elderly population in Japan increases, senile degenerative aortic valvular disease also tends to increase. These patients often have a small aortic annulus. The problem of "valve-patient-mismatch" occurs when a small prosthesis is inserted into a patient with a small aortic annulus. To avoid annular enlargement after aortic valve replacement (AVR), we tried to use a small-sized St. Jude Medical (SJM) valve. From September 1988 through November 1996, 110 AVR were performed in our institution. In these cases, 30 underwent AVR with a small sized SJM valve (male < or = 21 mm, female < or = 19 mm). Dobutamine stress echocardiography was performed in 19 patients who had undergone AVR with a small-sized SJM valve. Surgical results were also compared between patients with small aortic annulus and those with normal-sized aortic annulus. Using Doppler echocardiography, pressure gradients (PG), cardiac index (CI), effective orifice area (EOA), and performance index (PI) were calculated at rest and during stress. The mean body surface area (BSA) of patient who had undergone AVR with SJM19A, 19HP and 21A was 1.40, 1.42 and 1.56 m2, respectively. With dobutamine stress, heart rates, PG and CI increased significantly. Mean and maximum PG of patients with 19HP (8.0 and 15.4 mmHg at rest, 12.9 and 28.0 mmHg under stress, respectively) and 21A (9.5 and 19.1 mmHg at rest, 16.5 and 35.3 mmHg under stress, respectively) were relatively low. EOA index (EOAI) of patient with 19HP showed the highest values mean 0.93 cm2/m2. PIs tended to be higher with HP models than with standard models. The tests were completed without significant side effects such as frequent ventricular arrhythmias. Among the cases with small aortic annulus, there were no operative deaths or hospital deaths. There were also no late deaths, episodes of hemorrhage or thrombosis. Conclusions. In our institution, AVR was performed safely without any aortic annular enlargement with a small aortic anulus in small BSA patients. Postoperative hemodynamic data obtained by echocardiography were satisfactory for all patients at rest and even during maximum dobutamine stress test.

Aged↗
PubMed1998

Diffuse bilateral thalamic astrocytomas as examined serially by MRI.

We report the case of a 13-year-old girl with diffuse bilateral thalamic astrocytomas. Incoordination was observed at the onset. Cranial computed tomography (CT) showed enlarged thalami, and magnetic resonance imaging (MRI) revealed these lesions to be symmetrically enlarged with high intensity on the T2-weighted image. Owing to these atypical findings in the neuroimaging studies, we had difficulty in making the correct diagnosis of a brain tumor. After the diagnosis of diffuse bilateral thalamic astrocytomas was obtained, we performed hyperfractionated radiotherapy followed by chemotherapy. Radiation therapy was effective for a while, but the girl's condition deteriorated again and she died 8 months after admission. Although diffuse bilateral thalamic astrocytomas are difficult to diagnose because they do not resemble most other neoplasms on neuroimaging studies, pediatricians should keep this entity in mind in order to arrive at a precise and prompt diagnosis.

Adolescent↗
PubMed1998

Vulnerability to aging in the rat serotonergic system.

Distributional changes of serotonergic fibers associated with aging were demonstrated immunohistochemically. Old rat brains were morphologically characterized by the presence of peculiar features of serotonergic fibers not found in the young adult brain. In 24-month-old rats, these aberrant serotonergic fibers were subdivided into two groups according to morphological alterations: type 1 fibers consisting of thin fibers with moderately enlarged varicosities, and type 2 fibers consisting of much thicker fibers that have even larger varicosities and a tortuous course. These two types of fibers were distributed differentially in the forebrain. Type 1 fibers were found mainly in the striatum and frontoparietal cortex, whereas type 2 fibers were found in the posterior cingulate cortex and dentate gyrus of the hippocampal formation. Both types of aberrant fibers were seen in amygdala, frontoparietal cortex, hypothalamus, and thalamus. In 36-month-old rats, more highly degenerating arborizations were detected, and these aberrant ramifications were classified as follows based on shape as: type 3 fibers consisting of highly arborized thin fibers with a larger number of larger varicosities, and type 4 fibers consisting of thick fibers with abundant larger varicosities. Distributional difference indicated that type 1 fibers progress into type 3 fibers, whereas type 2 develop into type 4 fibers. These findings suggest the possibility that one set of pathological fibers emanate from the dorsal raphe nucleus and the other from the median raphe. Moreover, both two sets of serotonergic fibers show age-related aberrations in their morphology over same time course.

Aging↗