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Biomedical subjects

Y Takashima

Publications and source records attributed to Y Takashima.

At least 37 records · Page 2Linked to original sources

Whisker growth of l-menthol in coexistence with various excipients.

The purpose of the present study was to clarify the mechanism for l-menthol whisker growth. l-Menthol was mixed with an excipient, and the interaction was examined by IR measurement, thermal analysis and powder X-ray diffraction. Then we examined the involvement of the capillary condensation using the pore size distribution measurement. By mixing l-menthol with an excipient with whisker growth, the hydroxyl group stretching band of l-menthol was shifted to the higher wavenumber in the IR spectrum, the melting point and heat of fusion of l-menthol became lower in the thermal analysis, and the diffraction intensity of l-menthol became lower in the powder X-ray diffraction. The excipients with whisker growth showed the tendency to have the meso-pore involved in the capillary condensation in the pore size distribution measurement. From the above results, the whisker growth mechanism is considered as follows. When l-menthol was mixed with an excipient with whisker growth, the crystallinity of l-menthol was lowered and the vapor pressure was increased by the interaction mainly consisting of the hydrogen bond. The generated l-menthol vapor entered meso-pore, the saturated vapor pressure was lowered by the capillary condensation, and the nucleation occurred. The vapor was further supplied, generating the growth of whisker.

Crystallization↗

Nucleoredoxin, glutaredoxin, and thioredoxin differentially regulate NF-kappaB, AP-1, and CREB activation in HEK293 cells.

Well-established mechanisms for regulation of protein activity include thiol-mediated oxidoreduction in addition to protein-protein interactions and phosphorylation. Nucleoredoxin (NRX), glutaredoxin (GRX), and thioredoxin (TRX) have been shown to act as a potent thiol reductase and reactive oxygen species regulator. They constitute a oxidoreductase superfamily and have been suggested as a candidate operating in the redox regulation of gene expression. We demonstrated here that intracellular localization of these redox molecules differ from each other and that the redox molecules differentially regulate NF-kappaB, AP-1, and CREB activation induced by TNFalpha, PMA, and forskolin and by expression of signaling intermediate kinases, NIK, MEKK, and PKA in HEK293 cells. This is a first report that describes involvement of NRX and GRX and differences from TRX in transcriptional regulation of NF-kappaB, AP-1, and CREB in living cells.

3T3 Cells↗

Orbital cortex neuronal responses during an odor-based conditioned associative task in rats.

Neuronal activity in the rat orbital cortex during discrimination of various odors [five volatile organic compounds (acetophenone, isoamyl acetate, cyclohexanone, p-cymene and 1,8-cineole), and food- and cosmetic-related odorants (black pepper, cheese, rose and perfume)] and other conditioned sensory stimuli (tones, light and air puff) was recorded and compared with behavioral responses to the same odors (black pepper, cheese, rose and perfume). In a neurophysiological study, the rats were trained to lick a spout that protruded close to its mouth to obtain sucrose or intracranial self-stimulation reward after presentation of conditioned stimuli. Of 150 orbital cortex neurons recorded during the task, 65 responded to one or more types of sensory stimuli. Of these, 73.8% (48/65) responded during presentation of an odor. Although the mean breadth of responsiveness (entropy) of the olfactory neurons based on the responses to five volatile organic compounds and air (control) was rather high (0.795), these stimuli were well discriminated in an odor space resulting from multidimensional scaling using Pearson's correlation coefficients between the stimuli. In a behavioral study, a rat was housed in an equilateral octagonal cage, with free access to food and choice among eight levers, four of which elicited only water (no odor, controls), and four of which elicited both water and one of four odors (black pepper, cheese, rose or perfume). Lever presses for each odor and control were counted. Distributions of these five stimuli (four odors and air) in an odor space derived from the multidimensional scaling using Pearson's correlation coefficients based on behavioral responses were very similar to those based on neuronal responses to the same five stimuli. Furthermore, Pearson's correlation coefficients between the same five stimuli based on the neuronal responses and those based on behavioral responses were significantly correlated. The results demonstrated a pivotal role of the rat orbital cortex in olfactory sensory processing and suggest that the orbital cortex is important in the manifestation of various motivated behaviors of the animals, including odor-guided motivational behaviors (odor preference).

Animal Feed↗

Suppression of the proliferation of mouse splenocytes by pseudorabies virus.

Pseudorabies virus (PRV) infection in resistant swine caused immunosuppression which sometimes resulted in secondary infection by other viruses or bacteria. However the mechanism of the immunosuppression is not well understood. In this study, the effect of PRV on the immune system was examined in the mouse model. Splenocytes or lymphocytes prepared from the spleen of BALB/c mice were incubated in vitro with mitogen, and the ability of cells to proliferation was measured. When the cells were incubated with PRV, the ability of cells to proliferate was inhibited, although PRV did not multiply in the lymphocytes. UV-inactivated PRV also suppressed the proliferation of mice splenocyte. This result suggests that the structural component of PRV virion might cause the immunosuppression.

Animals↗

Ethical decision making and patient autonomy: a comparison of physicians and patients in Japan and the United States.

BACKGROUND: Patient-centered decision making, which in the United States is typically considered to be appropriate, may not be universally endorsed, thereby harboring the potential to complicate the care of patients from other cultural backgrounds in potentially unrecognized ways. This study compares the attitudes toward ethical decision making and autonomy issues among academic and community physicians and patients of medical center outpatient clinics in Japan and the United States. METHODS: A questionnaire requesting judgments about seven clinical vignettes was distributed (in English or Japanese) to sample groups of Japanese physicians (n = 400) and patients (n = 65) as well as US physicians (n = 120) and patients (n = 60) that were selected randomly from academic institutions and community settings in Japan (Tokyo and the surrounding area) and the United States (the Stanford/Palo Alto, CA, area). Responses were obtained from 273 Japanese physicians (68%), 58 Japanese patients (89%), 98 US physicians (82%), and 55 US patients (92%). Physician and patient sample groups were compared on individual items, and composite scores were derived from subsets of items relevant to patient autonomy, family authority, and physician authority. RESULTS: A majority of both US physicians and patients, but only a minority of Japanese physicians and patients, agreed that a patient should be informed of an incurable cancer diagnosis before their family is informed and that a terminally ill patient wishing to die immediately should not be ventilated, even if both the doctor and the patient's family want the patient ventilated (Japanese physicians and patients vs US physicians and patients, p < 0.001). A majority of respondents in both Japanese sample groups, but only a minority in both US sample groups, agreed that a patient's family should be informed of an incurable cancer diagnosis before the patient is informed and that the family of an HIV-positive patient should be informed of this disease status despite the patient's opposition to such disclosure (Japanese physicians and patients vs US physicians and patients, p < 0.001). Physicians in both Japan and the United States were less likely than patients in their respective countries to agree with physician assistance in the suicide of a terminally ill patient (Japanese physicians and patients vs US physicians and patients, p < 0.05). Across various clinical scenarios, all four respondent groups accorded greatest authority to the patient, less to the family, and still less to the physician when the views of these persons conflicted. Japanese physicians and patients, however, relied more on family and physician authority and placed less emphasis on patient autonomy than the US physicians and patients sampled. Younger respondents placed less emphasis on family and physician authority. CONCLUSIONS: Family and physician opinions are accorded a larger role in clinical decision making by the Japanese physicians and patients sampled than by those in the United States, although both cultures place a greater emphasis on patient preferences than on the preferences of the family or physician. Our results are consistent with the view that cultural context shapes the relationship of the patient, the physician, and the patient's family in medical decision making. The results emphasize the need for clinicians to be aware of these issues that may affect patient and family responses in different clinical situations, potentially affecting patient satisfaction and compliance with therapy.

Adolescent↗

[Pathogenesis of animal herpesviruses to human].

More than 90 spices of herpes viruses have been isolated from wide variety of non-human animals. Among these herpes viruses, only B virus (Cercopithecine herpesvirus 1), the natural host of which is macaque monkey, is severely pathogenic to human. B virus infects human through handling infected monkey tissues or by injury caused by infected monkey, and severe encephalitis ensues. However, in 1997 mucocutaneous infection without injury was reported. The genome structure and immunogenic property of B virus is similar to those of human herpesvirus(HSV). And pathogenecity of B virus to monkey is also similar to that of HSV to human. Although the natural host of pseudorabiesvirus (Suid herpesvirus 1) is swine, it infects wide range of animals and causes severe nervous symptoms. However, the pathogenicity to human is controversial.

Animals↗

Reduction of tablet coloration at tableting for oily medicine (tocopheryl nicotinate).

The powder (TN-PO) which adsorbed D,L-tocopheryl nicotinate (TN) as an oily medicine was prepared using porous calcium silicate (Florite(R)RE, FLR) as an adsorbing carrier. Tablets (TN-TAB) were produced by compression of TN-PO at different compression pressures. As TN-PO was compressed at the higher TN content in TN-PO and compression pressure, the more TN was exuded from TN-PO, and an increase in the degree of tablet coloration was observed. Therefore, FLR or colloidal silica (AEROSIL(R)200, AER) was newly added to TN-PO at compression to reduce the degree of tablet coloration. Further, the effects of addition of FLR or AER on the crushing strength, friability, porosity and disintegration property of the tablet and the dissolution property of TN from the tablet were studied. After addition of FLR or AER, a similar reduction of tablet coloration was observed. When the addition percentage of FLR to TN-PO exceeded 30%, the crushing strength of the tablet increased significantly. On the other hand, when TN-PO added with AER was compressed, no change was observed in the crushing strength of the tablet. The disintegration time of the tablet with added FLR was shorter than that of the tablet with added AER. At every addition percentage studied, the tablet with added FLR showed a higher releasing ability of TN compared with the tablet with added AER. These results indicate that it is possible to reduce tablet coloration by adding FLR or AER at compression of TN-PO. Further, it is considered that the differences in the crushing strength, disintegration property and dissolution property of TN between the tablets with added FLR or AER resulted in different liquid adsorbing and holding mechanisms of FLR particles and AER particles.

Antihypertensive Agents↗

Differential expression of glutaredoxin and thioredoxin during monocytic differentiation.

Macrophages generate reactive oxygen intermediates (ROIs) as the effectors of anti-bacterial defense mechanism. Intracellular ROIs and reduction/oxidation (redox) status play crucial roles in signal transduction. We therefore investigated the expression of redox-regulating proteins such as glutaredoxin (GRX) and thioredoxin (TRX) during the differentiation of murine monocytic leukemia cell line M1 cells and human monocytic leukemia cell line U937 cells. When M1 cells were treated by IL-6, GRX mRNA markedly increased and TRX mRNA also increased slightly. In contrast, there was no increase of GRX mRNA in D-cell, which is a sub-cell line derived from M1 lacking in the capacity of differentiation. GRX mRNA also increased in U937 cells differentiated by phorbol 12-myristate 13-acetate (PMA). By immunohistochemistry, unstimulated M1 cells showed strong staining of TRX and marginal staining of GRX. In contrast, TRX expression in IL-6 treated M1 cells is as strong as in unstimulated M1 cells, whereas GRX expression is slightly enhanced in IL-6 treated M1 cells. Phagocytosis is markedly enhanced and hydrogen peroxide production is slightly enhanced in IL-6 treated M1 cells. These results showed that TRX is steadily expressed whereas GRX is induced in association with the differentiation in macrophage-like cell line cells, suggesting differential roles of these redox regulators in macrophage lineage.

Animals↗

Identification of the US3 gene product of BHV-1 as a protein kinase and characterization of BHV-1 mutants of the US3 gene.

We have identified the product of the US3 gene of bovine herpes virus type 1 (BHV-1), which is homologous to the herpes simplex virus type 1 (HSV-1) US3 protein kinase (PK) gene. The antibodies against the BHV-1 US3 gene product reacted with a 58 kDa polypeptide in BHV-1 infected cells and the 58 kDa polypeptide purified by immuno-precipitation demonstrated PK activity. Recent reports indicating that the US3 gene of HSV-1 is involved in the blockage of apoptosis in virus infected cells. As to the apoptosis in BHV-1 infected cells, we found following: (1) no apoptosis was observed in cells infected with wild type BHV-1 and the US3 mutants (2) the apoptosis induced by the osmotic shock of sorbitol treatment was blocked when cells were infected by the wild type BHV-1 (3) the US3 mutants of BHV-1 blocked the apoptosis of sorbitol treated cell, but the suppressive effect was delayed relative to that of wild type BHV-1 (4) the other BHV-1 mutants, with the intact US3 gene but with some other non-essential gene (genes) deleted behaved similar way to the US3 mutant. It is concluded that the US3 gene of BHV-1 is not directly involved in the blockage of apoptosis in infected cells.

Animals↗

Growth behavior of bovine herpesvirus-1 in permissive and semi-permissive cells.

Bovine herpesvirus-1 (BHV-1) can replicate well in bovine-derived cell lines such as Madin Darby bovine kidney (MDBK) but grows poorly in hamster lung (HmLu-1). Virus replication, DNA synthesis, and immediate-early gene expression are severely restricted in HmLu-1. We compared adsorption and penetration of BHV-1 in permissive MDBK and semi-permissive HmLu-1 cells. At a low multiplicity of infection, BHV-1 attached to permissive MDBK cells twice as much as to HmLu-1. The presence of heparin inhibited the attachment of BHV-1 to MDBK cells by about 60%, but over 90% of the attachment was inhibited in HmLu-1. To investigate the penetration of BHV-1, we performed the quantitative measurement of viral DNA by quantitative competitive (QC)PCR in infected cells. In MDBK cells, virions attached to the cell surface, penetrated into the cells and were transported to the nucleus. However in HmLu-1, only a small fraction of the virions attached to the cell surface were allowed to penetrate. Our results indicated that the replication of BHV-1 in semi-permissive HmLu-1 was not dramatically restricted at one certain point but at some various stages including adsorption and penetration.

Animals↗

Problems and our solutions for implementing telemedicine systems.

There are several problems on the practical use of telemedicine, for example, the difficulties involved in promoting communication between medical facilities, uncooperative clinicians, and the absence of high-speed circuits and high-resolution CRT. From the Japanese point of view, we suggest ways to resolve these problems. We will analyze and propose scenarios for realizing successful communications among medical institutions, medical communication and its characteristics, barriers to the promotion of communications among medical institutions, second-opinion centers, and separate satellites and separate circuits. We also mention the World Wide Web for teleconsultation, provision of assistance to people with data handicaps via a communications satellite, and assistance to programs designed for training telemedicine specialists. Using a communication satellite, we offer programs that explain preventive medicine, support activities for nursing at home, explain the risks of fast food, and support activities for the handicapped and women in a simple manner to computer illiterates.

Communication↗

Molecular cloning, sequence analysis, and characterization of a penicillin-resistant DD-carboxypeptidase of Myxococcus xanthus.

We have cloned a gene, pdcA, from the genomic library of Myxococcus xanthus with an oligonucleotide probe representing conserved regions of penicillin-resistant DD-carboxypeptidases. The amino- and carboxy-terminal halves of the predicted pdcA gene product showed significant sequence similarity to N-acetylmuramoyl-L-alanine amidase and penicillin-resistant DD-carboxypeptidase, respectively. The pdcA gene was expressed in Escherichia coli, and the characteristics of the gene product were similar to those of DD-carboxypeptidase (VanY) of vancomycin-resistant enterococci. No apparent changes in cell growth, sporulation, or germination were observed in pdcA deletion mutants.

Amino Acid Sequence↗

Antiatherogenic effects of the antioxidant BO-653 in three different animal models.

Antioxidants have been proposed to have antiatherogenic potential by their inhibition of low density lipoprotein (LDL) oxidation. Here, we report an antioxidant, BO-653 (2,3-dihydro-5-hydroxy-2, 2-dipentyl-4,6-di-tert-butylbenzofuran), designed to exhibit antioxidative potency comparable to that of alpha-tocopherol, but yet possess a high degree of lipophilicity comparable to that of probucol. BO-653 exhibits a high affinity for LDL and is well distributed in aortic vessels in vivo. In atherosclerosis models of rabbits and mice, BO-653 has been shown to be able to suppress the formation of atherosclerotic lesions without untoward side effects. Specifically, there was no reduction of high density lipoprotein levels. This antioxidant provides additional evidence in support of the oxidized-LDL hypothesis, and itself is a promising candidate antioxidant for clinical use.

Animals↗

Ultrastructure of the foregut and associated glands in the lung fluke, Paragonimus miyazakii (Digenea: Troglotrematidae), with particular reference to their functional roles.

The foregut and associated glands of a digenetic trematode, Paragonimus miyazakii, were examined in the forebody by transmission and scanning electron microscopy as well as by light microscopy, and their functional roles were discussed. The foregut is lined with a general tegument without spines and sensory receptors throughout its length, although it consists of the mouth, pharynx, and esophagus. This foregut tegument is regionally and intraregionally modified in appearance, suggesting the performance of auxiliary functions in digestion. This appearance is characterized by long, frequent cytoplasmic extensions of the apical tegument around the middle portion of the mouth and the anterior esophagus. Electron-dense granules and multimembranous and multilamellar bodies are developed in the tegument to various degrees, and elaborately in the apical layer of the prepharynx. A single type of unicellular gland is embedded in the antero-middle part of the worm in small groups. The gland cells synthesize clear secretory granules as a chief product, each granule with a pleomorphic, dense, core-like inclusion. Mature granules are elliptical in shape, approximately 500 nm in diameter, and are subsequently discharged into the prepharyngeal foregut lumen after passing through the elongated cytoplasm of the gland cell. In the prepharynx and pharynx, host blood cells are apparently processed for digestion. In the wide lumen of the esophagus, foodstuff could undergo sufficient digestion prior to absorption by the cecal epithelium.

Animal Structures↗

Ocular hypotension induced by intravitreally injected C-type natriuretic peptide.

The purpose of the study is to determine if intravitreal injection of c-type natriuretic peptide (CNP) affects intraocular pressure (IOP), aqueous humor dynamics and guanosine 3',5'-cyclic monophosphate (cGMP) concentration in the aqueous humor of the rabbit eye. Also we investigated whether CNP-like immunoreactivities (CNP-LI) were present in porcine aqueous humor and whether CNP-LI were detected in rabbit and porcine ciliary body. The IOP was measured after intravitreal injection of 2 pmol approximately 20 nmol CNP into rabbit eyes. Aqueous humor dynamics (aqueous humor flow, outflow facility, and uveoscleral outflow) and cGMP concentration in the aqueous humor were determined at approximately 6 hr after CNP injection. The CNP concentration in aqueous was measured by radioimmunoassay in porcine eye, and CNP-LI were detected with a monoclonal antibody in porcine and rabbit eyes. Intravitreally injected CNP caused IOP reduction in a dose-dependent manner (P<0.0001) and the maximum effect was observed at 4 approximately 6 hr. CNP increased total outflow facility by approximately 35%, but did not affect aqueous humor flow or uveoscleral outflow. The cGMP concentration in the aqueous of CNP-treated eyes was about 4- to 14-fold higher than that in the contralateral untreated eyes. CNP concentration in aqueous was about 2-fold higher than that in plasma, and CNP-LI were found in non-pigmented epithelium of the ciliary body of both rabbit and porcine eyes. CNP may play an important role in the regulation of IOP.

Animals↗

Construction of canine herpesvirus vector expressing foreign genes using a lacZ-TK gene cassette as a double selectional marker.

An improved method for constructing canine herpesvirus (CHV) recombinants expressing foreign genes by using the lacZ-TK gene cassette as a double selectional marker was developed. A recombinant CHV carrying the lacZ-TK gene at a targeted gene locus was constructed and used as a parental virus for generating new recombinants. The parental virus formed blue plaques and was sensitive to TK-specific drugs, while newly generated recombinants, in which the lacZ-TK gene was replaced with the desired foreign gene, become both resistant to the TK-specific drugs and formed white plaques. Recombinants were isolated by using the combination of drug selection and color selection. This improved method allows construction of recombinant CHV with great ease, because the drug selection can enrich the frequency of recombinant CHV from 0.01-0.1% to 10-80%. This method was employed to construct a recombinant CHV that expressed rabies virus (RV) glycoprotein (G protein).

Animals↗

Qualitative and quantitative detection of cytomegalovirus DNA in sera by PCR as a clinical marker.

The amount of human cytomegalovirus (CMV) DNA in sera is considered to be a direct marker for CMV infection. We established conditions for nested PCR that detected one copy of CMV DNA, and for competitive PCR, which detected five or more copies of CMV DNA quantitatively. We tested 50 microl each of 16 freeze-stored and 5 fresh sera from patients, for CMV DNA. In sera obtained from the same patient at different time points, small amounts of CMV DNA were detected before the onset of CMV pneumonia. In sera from certain CMV-infected patients who were treated with the anti-CMV agent, ganciclovir, CMV DNA was not detected. Quantitative PCR detection of CMV DNA seems to be suitable for predicting early recurrent CMV infection and monitoring the efficacy of antiviral therapy. The qualitative nested PCR examination of CMV DNA in 40 cord blood plasma samples was carried out for the purpose of preventing CMV infection by cord blood stem cell transplantation, and they were all negative for CMV DNA.

AIDS-Related Opportunistic Infections↗