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Biomedical subjects

H Ozawa

Publications and source records attributed to H Ozawa.

At least 19 recordsLinked to original sources

Reduced phosphorylation of cyclic AMP-responsive element binding protein in the postmortem orbitofrontal cortex of patients with major depressive disorder.

In this study, we examined the amounts of cAMP-responsive element binding protein (CREB) and its phosphorylated form in homogenate preparations from postmortem orbitofrontal cortices of antidepressant drug-free patients with major depressive disorder and age-matched controls by immunoblotting. Immunoreactivies of both CREB and phosphorylated CREB were significantly decreased in depressive subjects compared to controls. The immunoreactivity of phosphorylated CREB was diminished to a greater extent than that of CREB in depressive patients. It has been indicated from animal studies that a transcription factor likely mediates neural plasticity in the mammalian brain and neural tissues. Our results suggest that alterations in the cAMP signaling system, especially in CREB, may be involved in the pathophysiology of depression and be potential targets for antidepressant treatment.

Aged↗

[Total arch replacement for right aortic arch with Kommerell diverticulum and aberrant left subclavian artery].

A 57-year-old man suspected of having angina pectoris underwent coronary angiography and comprehensive examination, which revealed a right-side aortic arch accompanying Kommerell diverticulum and a aberrant left subclavian artery. Esophagography indicated that the esophagus was compressed on its right posterior side and the computed tomography (CT) revealed that the posterior side of the tracheal was compressed, however, the patient experienced no difficulty in breathing, hoarseness of voice or dysphasia. The size of the aortic diverticulum was less than 5 cm and the patient showed no symptom, however, if it was left untreated, there was a risk of rupture in the future. Also the esophagus and tracheal may develop complications due to prolonged compression. Therefore, we decided that the case required surgical operation. Total arch replacement was performed through mediastinotomy and right posterolateral in the 4th intercostal. The postoperative condition was good, and the patient was discharged without any complications.

Aorta, Thoracic↗

Different modes of action of catecholamine-O-methyltransferase inhibitors entacapone and tolcapone on adenylyl cyclase activity in vitro.

Catechol-O-methyltransferase (COMT) inhibitors such as entacapone and tolcapone are used as adjuncts to L-DOPA ( l-3,4-dihydroxyphenylalanine, levodopa) in the treatment of Parkinson's disease. Tolcapone has been reported to associate with diarrhoea, a common reason for study withdrawal. The mechanism of this adverse effect is not yet understood. Cholera toxin causes diarrhoea by permanent activation of G(s) proteins, resulting in increased adenylyl cyclase (AC) activity. The aim of this study was to examine the effects of the COMT inhibitors entacapone and tolcapone on AC activity in membranes isolated from rat striatum, a brain structure enriched with dopaminergic G-protein-coupled receptors and AC activity. This study demonstrates differential effects of tolcapone and entacapone on Gpp(NH)p/dopamine-stimulated AC activity. Entacapone enhanced the stimulatory effect of Gpp(NH)p/dopamine, whereas tolcapone attentuated this effect, suggesting that diarrhoea associated with tolcapone treatment is not caused by permanent activation of G(s) proteins.

Adenylyl Cyclase Inhibitors↗

Effects of oestrogen deficiency on osteoclastogenesis in the rat periodontium.

This study was designed to investigate quantitative changes in osteoclast generation in rat periodontium following ovariectomy. Wistar rats, aged 9 weeks, were subjected to either ovariectomy (OVX) or sham surgery. Osmotic pumps were implanted in 24 rats and either 17beta-oestradiol or vehicle solution were infused continuously. The rats were assigned to one of the following groups: (1) OVX+vehicle; (2) sham+vehicle; or (3) OVX+ 17beta-oestradiol. On the days 7 and 14 after surgery, four rats in each group were killed. Mandibles were demineralized and embedded in paraffin. Frontal sections of alveolar bone in the region of the first molar were cut for enzyme histochemistry and immunohistochemistry. On day 7, there was no significant difference in the number of tartrate-resistant acid phosphatase (TRAP)-positive cells located on bone surfaces in either group. However, the number of TRAP-positive mononuclear cells that were separated from the bone surface was significantly higher in group 1 than in groups 2 and 3. On the day 14, the number of TRAP-positive cells in group 1, which were attached to the bone surface, was significantly higher than had been apparent on day 7. There were also significant increases in the number of nuclei of TRAP-positive cells attached to the bone in group 1 compared with groups 2 and 3 on day 14. These findings demonstrate that oestrogen deficiency induces of osteoclastogenesis in the rat periodontium and that quantitative changes in osteoclastogenesis could be prevented by E2 infusion.

Acid Phosphatase↗

Immunolocalization of osteoclast differentiation factor in rat periodontium.

The aim here was to observe the immunohistochemical localization of osteoclast differentiation factor (ODF)/receptor activator of NF kappa B ligand (RANKL) in the rat periodontium. Rat mandibles were demineralized and embedded in paraffin, and horizontal and frontal sections were prepared for immunohistochemical analysis. In horizontal sections, immunolocalization of RANKL was marked in the distal area of the periodontium of molars in which osteoclasts appeared, due to physiological tooth drift. In frontal sections, RANKL immunoreactivity was localized on spindle-shaped mesenchymal cells around blood vessels near the bone surface in the periodontium. In addition, immunoreaction for RANKL was detected on structures that appeared to be elongated cell processes near blood vessels in frontal sections. Immunohistochemical examination for the general antigen of nerve-specific protein suggested a similarity between these structures and nerve fibres.

Acid Phosphatase↗

Langerhans cell expression of neuropeptide Y and peptide YY.

Neuropeptide Y (NPY) and peptide YY (PYY) are structurally related peptides with a variety of known functions. The role of these peptides in the skin is largely unknown, although NPY-like immunoreactivity has been reported in the epidermis. The recent report that these peptides have antimicrobial properties suggests that NPY and PYY may contribute to the skin's defense mechanisms against invading microorganisms. We have demonstrated that Langerhans cells (LC) and a certain BALB/c epidermis-derived dendritic cell line contain mRNA for NPY and PYY using RT-PCR. Furthermore, this dendritic cell line as well as an epidermis-derived dendritic cell line from A/J mice were found to produce NPY and PYY and LC produced PYY, as assessed by radioimmunoassay. These data suggest that the protective function of LC include not only antigen presentation, but also production of antimicrobial peptides.

Animals↗

Effects of ovariectomy on trabecular structures of rat alveolar bone.

An association between postmenopausal osteoporosis and tooth loss has been proposed. However, histomorphometrical changes in alveolar bone following estrogen deficiency are rarely reported with data on microtrabecular structural changes. To clarify the relationship between estrogen deficiency and tooth loss, we histomorphometrically analyzed the trabecular structural changes of mandibular alveolar bone in ovariectomized rats. Twenty-four adult female Fischer rats were used. Eight rats were sacrificed on day 0 (baseline). The remaining 16 rats were divided into two groups. One group was ovariectomized bilaterally (OVX) and the other group was subjected to sham surgery (Sham). After administration of tetracycline and calcein, the animals were sacrificed 60 days after surgery. Bone histomorphometry, node-strut analysis and measurement of thickness of alveolar bone proper were performed on the interradicular septum of the first molar on the sagittal surface. The trabecular bone volume and trabecular number of the OVX group were significantly lower than those of the baseline and Sham groups. All of the bone resorptive and formative parameters of the OVX group were significantly higher (about one-and-a-half times) than those of the Sham group. Several osteoclasts were seen lining the irregular, eroded surface facing the bone marrow in the OVX group. Furthermore, the OVX group tended to have low microtrabecular stiffness and showed significantly thinner distal alveolar bone proper than in the baseline and Sham groups. In summary, estrogen deficiency caused osteoporotic changes and thin alveolar bone proper in the interradicular septum of rat first molar. This phenomenon might accelerate destruction of alveolar bone and tooth loss, especially in elderly women affected by periodontal disease.

Alveolar Process↗

Annexin-1 (lipocortin-1)-immunoreactivity in the folliculo-stellate cells of rat anterior pituitary: the effect of adrenalectomy and corticosterone treatment on its subcellular distribution.

In the pituitary gland, annexin-1 (lipocortin-1) located in folliculo-stellate (FS) cells has been advocated as one of the candidates for paracrine agents produced by FS cells that modulate the release of pituitary hormones. However, the expression and distribution pattern of annexin-1 in FS cells under different circulating corticosteroid conditions has not been examined. Thus, by means of pre-embedding immunoelectron microscopy, we investigated the expression of annexin-1 in FS cells under different corticosteroid conditions. Annexin-1-immunoreactivity was observed in the cytoplasm; especially intense immunoreactivity was detected in the follicle surface of FS cells under control conditions. After adrenalectomy, annexin-1-immunoreactivity almost disappeared, but the immunoreactivity recovered with corticosterone replacement. The expression of glucocorticoid receptor immunoreactivity in the nucleus of FS cells also showed a similar pattern to annexin-1 associated with the changes in the corticosteroid conditions. However, S-100 immunoreactivity, a marker for FS cells, was not changed whatever the corticosteroid conditions. These results confirm that glucocorticoids regulate the annexin-1 expression and demonstrate the translocation of annexin-1 from intracellular to pericellular sites in the FS cells of the rat anterior pituitary gland.

Adrenalectomy↗

Steroid effects on secretion from subsets of lactotrophs: role of folliculo-stellate cells and annexin 1.

Prolactin secretion is controlled by the hypothalamus, and by circulating steroids; oestrogens stimulate, but glucocorticoids inhibit prolactin release. Lactotrophs express intracellular receptors for oestrogens, but apparently not glucocorticoids. Therefore, a genomic effect of oestrogens could be direct, but that of glucocorticoids appears to be indirect. Lactotrophs are not a homogeneous cell population: some have large irregular dense-cored vesicles, others have small round vesicles, but the functional significance of this inhomogeneity is far from clear. Oestradiol and testosterone can stimulate rapid release of prolactin selectively from type II lactotrophs characterised by small round vesicles. Progesterone and other steroids do not exert this effect, which results from a non-genomic action of oestradiol and testosterone. Glucocorticoid inhibition of secretagogue-induced prolactin secretion is mimicked by annexin 1 (lipocortin 1), a protein induced by glucocorticoids in the pituitary and many other tissues, and can be blocked by annexin 1 immunoneutralisation and antisense. Glucocorticoid inhibition of ACTH and growth hormone secretion also involves annexin 1. Pituitary annexin 1 is located in folliculo-stellate cells; these express glucocorticoid receptors, and glucocorticoids induce annexin-1 synthesis. Annexin 1 is externalised from folliculo-stellate cells in response to glucocorticoids, despite the fact that it lacks a secretory signal sequence and is not packaged in vesicles. Inhibition of annexin 1 externalisation by glyburide suggests involvement of an ABC (ATP-binding cassette) transporter in externalisation. Both oestradiol and glucocorticoids therefore influence the secretion of prolactin by novel direct and indirect mechanisms, in addition to their much better understood effects on transcription via classical intracellular steroid receptors.

Animals↗

[Early and mid-term results of all arterial graft coronary artery bypass grafting using bilateral internal thoracic and radial arterial conduits].

From March 1996 to May 2000, 41 patients [age 39-78 (mean 63.5 +/- 8.8) years, 90.2% male] underwent all arterial multiple coronary artery bypass grafting (CABG) using bilateral internal thoracic (BiITA) and radial (RA) arterial conduits. The reason for using RA was that the right gastroepiploic artery (RGEA) was small or occluded on preoperative angiography, a history of upper abdominal surgery or disease, or the right coronary arterial lesion was proximal and mild. The BiITA were used as in situ grafts and the proximal anastomosis of RA was to the ascending aorta in all cases. All patients underwent conventional elective CABG with median sternotomy using cardiopulmonary bypass. The mean number of anastomoses was 3.3 +/- 0.5 branches and complete revascularization rate was 80.5%. Postoperative follow-up averaged 20 months and the longest was 50 months. There was no early death, and overall graft patency 2-3 weeks after surgery was 96.2% (LITA 94.0%, RITA 97.6%, RA 97.6%). Four-year actuarial survival rate was 96.4 +/- 3.5% (1 patient: 9 months, no cardiac death), and cardiac event-free rate after surgery was 89.7 +/- 4.9% [4 patients: percutaneous transluminal coronary angioplasty (PTCA)]. However, once patients were discharged from hospital, cardiac event-free rate was 100%. These excellent results suggest that all arterial graft CABG was satisfactory, and RA can be used as a third suitable arterial bypass conduit, if RGEA cannot be used or is unsuitable for use.

Adult↗

Immunohistochemical studies on the distribution of nerve fibers in the human prostate with special reference to the anterior fibromuscular stroma.

BACKGROUND: Although the anterior fibromuscular stroma (AFMS) comprises up to one third of the total bulk of the prostate, its physiological function remains unknown. We recently reported the possible contribution of the AFMS to micturition. The aim of this study is to reveal the differences in the distribution of innervation between the AFMS and the other regions of the prostate. METHODS: We performed immunohistochemical stainings using antibodies such as protein gene product (PGP) 9.5, tyrosine hydroxylase(TH), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP). Morphometric analysis was made to examine the density of peripheral nerve fibers containing PGP 9.5, TH, NPY, and VIP by using a computer-assisted imaging system. RESULTS: The number of PGP 9.5-immunoreactive (IR) nerve fibers and the smooth muscle in the AFMS decreased from the base to the apex of the prostate. TH-IR nerve fibers were more abundant in the AFMS than in the transition zone. NPY- and VIP-IR nerve fibers were less numerous in the AFMS than in the peripheral zone. CONCLUSIONS: This study is the first to demonstrate that the AFMS has peculiar neuronal innervation. We observed significantly different innervation in the AFMS compared with the other regions of the prostate.

Aged↗

Thermodynamics of fluid turbulence: a unified approach to the maximum transport properties.

Dissipative properties of various kinds of turbulent phenomena are investigated. Two expressions are derived for the rate of entropy increase due to thermal and viscous dissipation by turbulence, and for the rate of entropy increase in the surrounding system; both rates must be equal when the fluid system is in a steady state. Possibility is shown with these expressions that the steady-state properties of several different types of turbulent phenomena (Bénard-type thermal convection, turbulent shear flow, and the general circulation of the atmosphere and ocean) exhibit a unique state in which the rate of entropy increase in the surrounding system by the turbulent dissipation is at a maximum. The result suggests that the turbulent fluid system tends to be in a steady state with a distribution of eddies that produce the maximum rate of entropy increase in the nonequilibrium surroundings.

Journal Article↗

Induction of cysteine string protein after chronic antidepressant treatment in rat frontal cortex.

We have previously identified 204 partial cDNA fragments (ADRG1-204) as antidepressant related genes/expressed sequence tags. Then, we developed our original cDNA microarrays, on which the 194 clones out of ADRG1-204 were spotted. With this ADRG microarray, we found that the expression of a spot, ADRG55, which representing cysteine string protein (CSP), was significantly increased in rat brain after chronic treatment with a selective serotonin reuptake inhibitor, sertraline. In the present study, reverse transcription-polymerase chain reaction analysis confirmed the induction of CSP at mRNA levels in rat frontal cortex after chronic treatment with two different classes of antidepressants, imipramine or sertraline. Western blot analysis also revealed that CSP-immunoreactivity was increased after antidepressant treatment. In conclusion, our data suggest that CSP is one of the common functional molecules induced after chronic antidepressant treatment.

Animals↗

Increased levels of calcium-sensitive adenylyl cyclase subtypes in the limbic system of alcoholics: evidence for a specific role of cAMP signaling in the human addictive brain.

We examined the amounts of several adenylyl cyclase (AC) isoforms and of cAMP-response element binding protein (CREB) in alcoholic and control brains. Immunoreactivity of type I AC was significantly increased in alcoholic nucleus accumbens and corpus amygdaloideum. Immunoreactivity of type VIII AC was also increased in alcoholic corpus amygdaloideum and hippocampus. CREB immunoreactivities were unchanged. These findings indicate that the brain-region specific increase of Ca(2+)-sensitive AC may contribute to the pathophysiology of alcoholism.

Adenylyl Cyclases↗

Collective inhibition of pRB family proteins by phosphorylation in cells with p16INK4a loss or cyclin E overexpression.

The activity of the retinoblastoma protein pRB is regulated by phosphorylation that is mediated by G(1) cyclin-associated cyclin-dependent kinases (CDKs). Since the pRB-related pocket proteins p107 and p130 share general structures and biological functions with pRB, their activity is also considered to be regulated by phosphorylation. In this work, we generated phosphorylation-resistant p107 and p130 molecules by replacing potential cyclin-CDK phosphorylation sites with non-phosphorylatable alanine residues. These phosphorylation-resistant mutants retained the ability to bind E2F and cyclin. Upon introduction into p16(INK4a)-deficient U2-OS osteosarcoma cells, in which cyclin D-CDK4/6 is dysregulated, the phosphorylation-resistant mutants, but not wild-type p107 or p130, were capable of inhibiting cell proliferation. Furthermore, when ectopically expressed in pRB-deficient SAOS-2 osteosarcoma cells, the wild-type as well as the phosphorylation-resistant pRB family proteins were capable of inducing large flat cells. The flat cell-inducing activity of the wild-type proteins, but not that of the phosphorylation-resistant mutants, was abolished by coexpressing cyclin E. Our results indicate that the elevated cyclin D- or cyclin E-associated kinase leads to systemic inactivation of the pRB family proteins and suggest that dysregulation of the pRB kinase provokes an aberrant cell cycle in a broader range of cell types than those induced by genetic inactivation of the RB gene.

Cyclin E↗