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Biomedical subjects

Y Murakami

Publications and source records attributed to Y Murakami.

At least 469 records · Page 26Linked to original sources

Antibody responses and protection in mice immunized orally against influenza virus.

Antibody responses and protection were studied in BALB/c mice immunized orally with formalin-inactivated influenza viruses (A/PR/8/34) combined with cholera toxin B subunit as adjuvant. Influenza virus-specific IgA as well as IgG antibody responses were induced in the mice, depending on the oral dosage frequency. The oral immunization by multiple doses resulted in reduction of viral replication in the nose and prevention of development of infection in the lung after intranasal (i.n.) challenge. The protective effect in the nose was thought to be related to the nasal IgA antibody response. The oral immunization was, however, less efficient for induction of the IgA antibody response and protection in the nose, compared with an i.n. immunization. The oral immunization following subcutaneous priming led to the complete protection in the nose, accompanied-by a prompt local IgA antibody response.

Adjuvants, Immunologic↗

Analysis of defense mechanisms against bacterial infection by oral streptococcus in normal flora.

The incidence of oral alpha-streptococci with inhibitory activity against pathogens as a defense mechanism in the oral cavity was investigated in healthy individuals. Inhibitory strains were isolated from tonsil, tongue, cheek, saliva and dental plaque, and the detection rate of these strains isolated from tonsil was the highest. These results suggested that tonsillar flora is most important as a defense mechanism of the oral cavity. With respect to the effects of antibiotics against inhibitory alpha-streptococci, minimal inhibitory concentration of 90% of cells (MIC90) of PCG, ABPC, CCL, CFIX and EM against inhibitory alpha-streptococci, and relative detection rates of inhibitory alpha-streptococci before and after antimicrobial therapy were investigated. MIC90s of all antibiotics against these strains were low and sensitive to antibiotics tested. However, in vivo, detection rates of these strains before and after therapy did not differ significantly. Therefore, inhibitory strains were not affected by antibiotics as their MIC90 were low during short term medication.

Adult↗

Permeation from the synovial fluid as nutritional pathway for the anterior cruciate ligament in rabbits.

The anterior cruciate ligament of the knee receives its nutrition from a direct vascular supply and by permeation of nutrients from synovial fluid. In order to quantitate the relative importance of these two routes and to compare the anterior cruciate ligament with the medial collateral ligament, we injected [3H]methyl-glucose as a tracer intravenously or directly into the knee in rabbits. Tracer concentrations in plasma, synovial fluid, the anterior cruciate ligament and the medial collateral ligament were analysed by a pharmacokinetic compartment model developed for this study. The contribution of [3H]methyl-glucose permeation from the synovial fluid was calculated at 59.7% in the anterior cruciate ligament and at 18.1% in the medial collateral ligament. We concluded from these results that the nutrition for the medial collateral ligament, which is an extraarticular structure, is provided mainly by its vascular supply. In contrast, synovial fluid permeation is an important transport route for small molecules for the normal anterior cruciate ligament.

Animals↗

A nonneuronal isoform of cell adhesion molecule L1: tissue-specific expression and functional analysis.

The cell adhesion molecule L1 is a multifunctional protein in the nervous system characterizing cell adhesion, migration, and neurite outgrowth. In addition to full-length L1, we found an alternatively spliced variant lacking both the KGHHV sequence in the extracellular part and the RSLE sequence in the cytoplasmic part of L1. This L1 variant was expressed exclusively in nonneuronal cells such as Schwann cells, astrocytes, and oligodendrocytes, in contrast to the expression of the full-length L1 in neurons and cells of neuronal origin. To investigate the functions of the L1 variant, we established cell lines transfected with a cytoplasmic short L1 (L1cs) cDNA that lacks only the 12-bp segment encoding for the RSLE sequence. The promoting activities of homophilic cell adhesion, neurite outgrowth, and neuronal cell migration of L1cs-transfected cells (L4-2) were similar to those of full-length L1-transfected cells (L3-1), but the cell migratory activity of L4-2 itself was clearly lower than that of L3-1. In conclusion, the short form of L1 is a nonneuronal type, in contrast to the neuronal type of the full-length L1. Deletion of the four amino acids RSLE in the cytoplasmic region of L1 markedly reduced cell migratory activity, suggesting an importance of the RSLE sequence for the signaling events of neuronal migration mediated by L1.

Amino Acid Sequence↗

Age-related alterations in the auditory brainstem responses and the compound action potentials in guinea pigs.

The auditory brainstem response (ABR) and the eight nerve compound action potential (CAP) were measured using click click stimuli to investigate the age-related alteration in the auditory function in 66 guinea pigs consisting of four age groups. With advancing age, a gradual elevation of the thresholds in both the ABR and CAP was clearly seen, together with the prolonged latencies for waves I, II, III, and IV to clicks at 95 dBpeSPL in the ABR. There were some individual differences in either threshold elevation or latency prolongation of both the ABR and CAP in aged guinea pigs. These findings suggest that the effect of individual differences on degenerative aging processes of the auditory system should be considered in selected aged animals, although a significant elevation of the neural auditory threshold is clearly found with advancing age as a whole.

Action Potentials↗

Deletion mapping of chromosome 10 in human glioma.

We analyzed DNAs from 35 gliomas (27 malignant, grades III and IV; 8 less malignant, grades I and II) for loss of heterozygosity (LOH) using microsatellite sequences on chromosome 10 as polymorphic markers. An LOH was found in 8 of 11 (73%) glioblastomas (grade IV) and 4 of 16 (25%) grade III gliomas, but not in the less malignant types. We detected three commonly deleted regions. One was located in a telomeric region of 10p and the others were relatively large regions of 10q. Our results suggested that three putative tumor suppressor genes on chromosome 10 are involved in the malignant progression of gliomas.

Alleles↗

Psychosomatic aspects of healthy young women with orthostatic dysregulation.

The Japanese Edition of the Cornell Medical Index-Health Questionnaire and the Yatabe-Guilford personality test (Y-G Test) was given to 56 young women (mean age 19.2 years) who were identified as having orthostatic dysregulation among a total of 280 healthy young women. The percentage classed as types III (possible neurotic) and IV (probable neurotic) according to the Health Questionnaire was 37.5% in the 56 with orthostatic dysregulation and 9.2% in the controls (n = 65). The percentage classed as types B and E, suggestive of emotional or psychological disturbance according to the personality test, was 59.0% in those with orthostatic dysregulation and 23.1% in the controls. These differences were statistically significant (P < 0.01). Furthermore, there was a significant correlation (P < 0.01) between the two test results for the frequency distribution of the 280 women. These results suggest a possibility that psychosomatic factors influence the occurrence of orthostatic dysregulation in young women, even if these subjects have not sought treatment for dizziness or vertigo, nor for psychosomatic disorders.

Adult↗

Sensitization of T-cell receptor-alpha beta+ T cells recovered from long-term T-cell receptor downmodulation.

Although the survival of fully allogeneic skin grafts was prominently prolonged by adult thymectomy in anti-T-cell receptor-alpha beta monoclonal antibody (TCR-alpha beta mAb)-treated mice compared with that of non-adult thymectomized (ATX) mice, the skin allografts were eventually rejected. In the anti-TCR-alpha beta mAb-treated ATX mice, as shown in the present study, most of TCR-alpha beta+ cells were promptly activated on day 2 and then rapidly disappeared by day 7, but some TCR-alpha beta- Thy-1+ cells remained at that time. These TCR-alpha beta- Thy-1+ cells which have downmodulated their TCR-alpha beta expression may be refractory to depletion events by the mAb treatment. Although these downmodulated T cells re-expressed their TCR-alpha beta on day 50, they could not respond to stimuli via TCR such as TCR cross-linking or alloantigens. However, they recovered the reactivity to donor antigens on day 85. These results indicate that the downmodulated T cells by anti-TCR-alpha beta mAb treatment are long-lived and re-express their TCR-alpha beta at a late stage to be sensitized to donor antigen, which suggests that additional regimens may be required to get permanent, or very long-term, graft acceptance.

Animals↗

Intellectual development of offspring of diabetic mothers.

We prospectively evaluated the intellectual development of 33 children who were born to 33 diabetic Japanese mothers and compared them to 34 children born to non-diabetic mothers (controls) during the same period at Kurume University Hospital between 1987 and 1989. Birthweight, maternal age and the infant's age at the time of intelligence testing did not differ significantly between the offspring of diabetic mothers (ODMs) and controls. Tanaka-Binet intelligence scores were significantly lower in the ODMs at 3 years of age than in controls (98.4 +/- 17.4 versus 113.4 +/- 15.3) (p = 0.0005). No correlation was found between IQ and maternal haemoglobin A1c levels during pregnancy. Maternal age and infant IQ were inversely correlated in ODMs (p = 0.0298, r = -0.3984), but no such correlation was demonstrated in the controls. The results indicated that the ODMs may show a poorer intellectual development than those of non-diabetic mothers.

Child Development↗

Tetrahydrobiopterin and GTP cyclohydrolase I in a rat model of endotoxic shock: relation to nitric oxide synthesis.

Induction of the inducible isoform of nitric oxide synthase (iNOS) in various types of cells is implicated as the cause of septic shock. We evaluated the concentration of tetrahydrobiopterin (BH4), a cofactor of NOS, in plasma and various other tissues of rats treated with lipopolysaccharide (LPS; 10 mg/kg I.V.). The activity of GTP cyclohydrolase I (GTPCH), the first and rate-limiting enzyme in the de novo synthesis of BH4, in rat tissues was also determined. Three hours after administration of LPS, rats showed plasma levels of BH4 and NOx (NO3- and NO2-) that were elevated by 137 and 206%, respectively. GTPCH was expressed in liver and, to a lesser extent, in the lung, heart and kidney of control rats. In control rats, although a high concentration of BH4 was detected in the liver, its level was lower in lung, heart, kidney and aorta. Three hours after LPS administration, a significant increase in BH4 concentration and/or GTPCH activity was observed in all tissues examined except the liver. Our results demonstrate that the de novo synthesis of BH4 is upregulated by LPS in the rat in vivo, which may, at least in part, account for the increases in plasma level and tissue concentration of BH4 after the administration of LPS.

Anesthesia, General↗

Basic imaging properties of a new screen-film system for chest radiography.

To evaluate the potential clinical usefulness of a new screen-film system (advanced screen-film system; AD system) for chest radiography, its fundamental imaging properties compared with a conventional screen-film system (HR-4/HR-S) were investigated. The basic imaging properties were evaluated by measuring characteristic (H&D) curves, relative speeds, MTFs (modulation transfer functions), WS (Wiener spectra), and x-ray attenuations of screens. The detail visibilities and pathological details of various diseases in chest radiographs of patients were evaluated subjectively. The film gradient of the AD system was slightly lower at low radiographic density, and higher at high density, as compared with a conventional screen-film system. The screen speed of the AD system was 212% greater than that of the conventional system, and the film speed was 53% that of the conventional film. As the result, the total speed of the AD system was slightly higher compared with the conventional system. The spatial resolution of the AD system was comparable to or slightly lower than that of the conventional system. The noise level of the AD system was considerably lower than that of the conventional system at low (D = 0.5) and middle (D = 1.0) radiographic density levels. However, it was high at high radiographic density (D = 1.8). The radiographic densities in the underpenetrated areas with the AD system were greater than those of the conventional system when the lung densities are matched comparable. Improvement in noise level with the AD system at low and middle density levels may be useful for detection of various diseases in chest radiographs.

Equipment Design↗

Biosynthesis of Poly(3-Hydroxyalkanoic Acid) Copolymer from CO(inf2) in Pseudomonas acidophila through Introduction of the DNA Fragment Responsible for Chemolithoautotrophic Growth of Alcaligenes hydrogenophilus.

Pseudomonas acidophila is a bacterial strain producing a poly(3-hydroxyalkanoic acid) (PHA) copolymer from low-molecular-weight organic compounds such as formate and acetate. The genes responsible for PHA production were cloned in cosmid pIK7 containing a 14.8-kb HindIII fragment of P. acidophila DNA. With the aim of developing a means of producing a PHA copolymer from CO(inf2), cosmid pIK7 was introduced into a polymer-negative mutant of the chemolithoautotrophic bacterium Alcaligenes eutrophus PHB(sup-)4. However, the recombinant strain produced a homopolymer of 3-hydroxybutyric acid (polyhydroxybutyric acid) from CO(inf2). Since it was thought that the composition of the accumulated polymer might depend not on the PHA biosynthetic genes but on the metabolism of the host strain, a recombinant plasmid, pFUS, containing the genes for chemolithoautotrophic growth of the hydrogen-oxidizing bacterium A. hydrogenophilus was introduced into P. acidophila by conjugation. The recombinant plasmid pFUS was stably maintained in P. acidophila in the absence of chemolithoautotrophic or antibiotic selection. This pFUS-harboring strain possessed the ability to grow under a gas mixture of H(inf2), O(inf2), and CO(inf2) in a mineral salts medium, and PHA copolymer accumulation was confirmed by nuclear magnetic resonance spectral analysis. A gas chromatogram obtained by gas chromatography-mass spectrometry showed the composition of the polymer to be 52.8% 3-hydroxybutyrate, 41.1% 3-hydroxyoctanoate, and 6.1% 3-hydroxydecanoate. This is the first report of the production of a PHA copolymer from CO(inf2) as sole carbon source.

Journal Article↗

Porphyromonas gingivalis fimbrillin is one of the fibronectin-binding proteins.

In this study, we demonstrate that Porphyromonas gingivalis fimbrillin, a major component of bacterial fimbriae, is one of the fibronectin-binding proteins and that fibronectin is a potent inhibitor of the adherence of the bacteria to host cells and of the pathogenesis of the bacterium that acts by binding to the fimbriae. A Western blotting (immunoblotting) assay showed that fibronectin binds strongly to P. gingivalis fimbrillin. The fimbrial binding to fibronectin was also evidenced by a binding assay involving 125I-labeled fimbriae. Furthermore, fibronectin markedly inhibited the fimbria-induced expression of interleukin-1beta and neutrophil-specific chemoattractant KC genes in macrophages. The inhibitory action depended on the fimbrial interaction with heparin-binding and cell attachment domains in the fibronectin structure. The binding of P.gingivalis to mouse peritoneal macrophages via its fimbriae was inhibited by fibronectin. Fibronectin also inhibited the bacterial cell-induced expression of interleukin-1beta and KC genes in the macrophages. These results demonstrate the importance of fibronectin as a modulator of the pathogenic mechanism of P. gingivalis, a pathogen that causes adult periodontal disease.

Adhesins, Bacterial↗

Effects of platelet activating factor on mucociliary clearance of the eustachian tube.

The effects of platelet activating factor (PAF) on mucociliary clearance of the eustachian tube were investigated both in vitro and in vivo. Normal ciliated epithelium was obtained from the eustachian tube of guinea pigs and incubated with PAF at concentrations ranging from 10(-10) to 10(-6) mol/L. Ciliary activity was observed under an inverted microscope and quantified photoelectrically. The PAF dose-dependently inhibited ciliary activity. One milliliter each of 10(-5) mol/LPAF, 10(-5) mol/L prostaglandin E2 (PGE2), 10(-5) mol/LPAF and PGE2, or the control solution (0.1 v/v% methanol-phosphate-buffered saline) was directly injected into the tympanic bullae of anesthetized chinchillas. The middle ear was examined by otomicroscopy, tympanometry, and auditory brain stem response in relation to time. The PAF delayed middle ear clearance, and the PGE2 augmented its delay. These findings suggest that PAF inhibits mucociliary clearance of the eustachian tube from the middle ear, and that PGE2 plays an important role in the augmentation of inflammatory disorders.

Animals↗

Involvement of pituitary adenylate cyclase-activating polypeptide in growth hormone secretion induced by serotoninergic mechanisms in the rat.

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) stimulated GH secretion in superfused rat anterior pituitary cell in vitro and in conscious male rats in vivo. PACAP-38-induced GH secretion was inhibited by PACAP-(6-38), an N-terminal-deleted analog, at 100-fold concentrations of PACAP-38 both in vitro and in vivo. In contrast, a GH-releasing hormone antagonist did not affect the action of PACAP-38 to stimulate GH release in vitro. Plasma GH increase induced by i.v. injection of 5-hydroxy-L-tryptophan (1 mg/100 g BW), a precursor of serotonin, was blunted by PACAP-(6-38) (1 nmol/100 g BW, i.v.), whereas spontaneous pulsatile GH secretion in conscious male rats, which is governed by hypothalamic GH-releasing hormone and somatostatin, was not affected by repeated i.v. injection of PACAP-(6-36). These findings suggest that PACAP-(6-38) is a potent antagonist of PACAP-38 to stimulate GH secretion both in vivo and in vitro. Taken together with the facts that PACAP-38 is highly concentrated in the hypothalamus and that is released into the hypophysial portal blood, our present findings suggest that PACAP-38 might play a stimulatory role on GH secretion induced by serotoninergic mechanisms in the rat.

5-Hydroxytryptophan↗

A variant of adenomatous goiter with characteristic histology and possible hereditary thyroglobulin abnormality.

A variant type of adenomatous goiter was identified in 24 of 2160 patients with adenomatous goiter who underwent thyroidectomy. The characteristics of the thyroid gland in these 24 patients included large goiter, small follicles, scant colloid, and columnar follicular cells containing yellow-green granules on hematoxylin-eosin staining. The thyroid gland was slightly orange-red, and electron microscopic examination showed abundant lysosomes with colloid droplets. When comparing the features of this group with those of 24 patients with common adenomatous goiter, the incidence of familial predisposition to thyroid diseases in the former group was higher. The age at the time of detection of goiter was lower, i.e. 17 +/- 15 vs. 44 +/- 17 yr (P < 0.001, variant type vs. common type), the serum total T4 concentrations were lower (84 +/- 21 vs. 103 +/- 18 nmol/L; P < 0.01), and the serum TSH concentrations were higher (2.4 +/- 2.1 vs. 1.0 +/- 0.9 mU/L; P < 0.01). Thyroid radioiodine uptake was remarkably increased (49 +/- 22 vs. 16 +/- 9%; P < 0.001), and lower levels of serum thyroglobulin were noted (33 +/- 51 vs. 484 +/- 603 micrograms/L; P < 0.01). The thyroglobulin content was low in the thyroid gland studied. The data suggest that the etiology of this variant type of goiter is a hereditary abnormality in thyroglobulin synthesis, and this type of goiter may be distinguished from common adenomatous goiter by the characteristic morphology of the thyroid gland in addition to clinical findings.

Adult↗

Changes in thyroid volume in response to radioactive iodine for Graves' hyperthyroidism correlated with activity of thyroid-stimulating antibody and treatment outcome.

This study investigated 1) the relationship between thyroid volume and thyroid function in radioactive iodine (RAI) treatment for Graves' disease, and 2) the activity of thyroid-related Ig in serum on the responsiveness of thyroid tissue to RAI. The changes in thyroid volume per megabecquerel (MBq) of 131I retained in thyroid tissue was calculated by ultrasonography as a quantitative indicator of the effect of RAI on thyroid volume. Of the 52 patients treated with 131I (3.7 MBq retained/g thyroid tissue), 26 patients showed thyrotoxicosis, 20 patients became euthyroid, and 6 patients developed hypothyroidism 6 months after therapy. The change in thyroid volume per MBq 131I was lower (P < 0.01) in the hyperthyroid patients than in the euthyroid or hypothyroid patients. The activity of thyroid-stimulating antibody in serum immediately before the therapy was greater (P < 0.01) in the hyperthyroid patients than in the euthyroid patients and was greater (P < 0.05) in the euthyroid patients than in the hypothyroid patients; it was inversely correlated with the changes in thyroid volume per MBq 131I (r = -0.667; P < 0.01). Accurate measurement of changes in thyroid volume during the course of RAI treatment provides evidence of the responsiveness of Graves' disease thyroid tissue to RAI, which is related to the outcome of thyroid function. Thyroid-stimulating antibody determination may be useful in deciding the appropriate dose of RAI to obtain euthyroidism instead of hyperthyroidism.

Adult↗

Molecular cloning of a complementary DNA for a membrane cofactor protein (MCP, CD46)/measles virus receptor on Vero cells and its functional characterization.

We isolated a 1257-bp cDNA encoding a membrane cofactor protein (MCP, CD46)/measles virus (MV) receptor-like protein from a cDNA library of Vero cells, in which wild MV strains were established. Vero cells contain MCP mRNA splice products encoding different cytoplasmic tails like human cells. The deduced amino acid sequence of the cDNA was 86% identical to that of human MCP. Vero cell MCP expressed on CHO cells was recognized by monoclonal antibodies against human MCP, and served as a potent MV receptor. In addition, Vero MCP was as effective as human MCP in human factor I-mediated C3b cleavage. Thus, the high MV susceptibility of Vero cells can in part be attributed to an MCP-like molecule that is structurally and functionally similar to human MCP.

Amino Acid Sequence↗