PubMed Health⌕ Search

Biomedical subjects

Hitoshi Okamura

Publications and source records attributed to Hitoshi Okamura.

At least 19 recordsLinked to original sources
PubMed2007

Factors related to anxiety and depression in women with breast cancer and their husbands: role of alexithymia and family functioning.

GOALS OF WORK: The purpose of this study was to explore alexithymia, family functioning, and other factors that might affect anxiety and depression levels in women with breast cancer and in their husbands. PATIENTS AND METHODS: A cross-sectional study was undertaken in 46 postsurgical ambulatory women with breast cancer and their husbands. Documented informed consent for the study was obtained from each subject. All subjects completed the Zung self-rating anxiety scale (SAS), the Zung self-rating depression scale (SDS), the 20-item Toronto alexithymia scale (TAS-20), and the family assessment device (FAD). MAIN RESULTS: Multiple regression analysis revealed that a high degree of alexithymia in patients correlated with a high degree of patient anxiety. Patient perceptions of inappropriate affective responsiveness among family members correlated with a high degree of depression. Among husbands, a high degree of anxiety was correlated with their own high level of alexithymia or low level of education, and with the occurrence of adjuvant therapy in their wives. Husband perceptions of inappropriate sharing of roles among family members, their own low education level, and a large number of family members correlated with high degrees of depression among them. CONCLUSIONS: The present study revealed that alexithymia and family functioning are associated with anxiety and depression, respectively, in both women with breast cancer and in their husbands. Individual traits such as alexithymia and family functioning should be taken into account when we intervene to treat anxiety and depression in breast cancer patients and their husbands.

Affective Symptoms↗
PubMed2006

Factors related to posttraumatic stress in adolescent survivors of childhood cancer and their parents.

GOALS OF WORK: The purpose of this study was to investigate factors related to severe posttraumatic stress symptoms (PTSS) in adolescent survivors of childhood cancer and their parents. MATERIALS AND METHODS: Eighty-nine families (88 adolescent survivors of childhood cancer, 87 mothers, 72 fathers) completed a self-report questionnaire. Multivariate logistic regression analyses were performed using the following risk factors for severe PTSS: trait anxiety, family functioning, demographic and medical variables. MAIN RESULTS: Severe PTSS were reported by 10.9% (n=9) of the survivors, 20.7% (n=18) of the mothers, and 22.2% (n=16) of the fathers. Preliminary analyses found significant correlations of PTSS between mother-survivor (Spearman's gamma=0.377, p<0.01) and mother-father (Spearman's gamma=0.483, p<0.01). The results of multivariate analyses indicated that higher trait anxiety [odds ratio (OR):1.16; 95% confidence interval (CI): 1.03-1.31; p<0.05] and having medical sequelae (OR: 5.85; 95% CI:1.02-33.72; p<0.05) were significant factors related to PTSS for survivors. For mothers, the significant PTSS-related factors were: higher trait anxiety (OR:1.13; 95% CI:1.04-1.23; p<0.01); 5- to 9-year interval from the first diagnosis to the present investigation, compared to more than a 10-year interval (OR: 6.45; 95% CI:1.67-24.89; p<0.01); and a relatively lower rating on "roles" of family functioning (OR: 12.34; 95% CI:1.11-136.97; p<0.05). For fathers, trait anxiety was a significant related factor (OR: 1.07; 95% CI:1.01-1.14; p<0.05). CONCLUSIONS: Survivors and their parents suffered from PTSS after long interval from completion of treatment, and PTSS-related factors varied for each family member. Appropriate allocation of responsibility for family functioning may promote the ability to decrease PTSS, especially for mothers.

Adaptation, Psychological↗
PubMed2006

V1a vasopressin receptors maintain normal blood pressure by regulating circulating blood volume and baroreflex sensitivity.

Arginine-vasopressin (AVP) is a hormone that is essential for both osmotic and cardiovascular homeostasis, and exerts important physiological regulation through three distinct receptors, V1a, V1b, and V2. Although AVP is used clinically as a potent vasoconstrictor (V1a receptor-mediated) in patients with circulatory shock, the physiological role of vasopressin V1a receptors in blood pressure (BP) homeostasis is ill-defined. In this study, we investigated the functional roles of the V1a receptor in cardiovascular homeostasis using gene targeting. The basal BP of conscious mutant mice lacking the V1a receptor gene (V1a-/-) was significantly (P < 0.001) lower compared to the wild-type mice (V1a+/+) without a notable change in heart rate. There was no significant alteration in cardiac functions as assessed by echocardiogram in the mutant mice. AVP-induced vasopressor responses were abolished in the mutant mice; rather, AVP caused a decrease in BP, which occurred in part through V2 receptor-mediated release of nitric oxide from the vascular endothelium. Arterial baroreceptor reflexes were markedly impaired in mutant mice, consistent with a loss of V1a receptors in the central area of baroreflex control. Notably, mutant mice showed a significant 9% reduction in circulating blood volume. Furthermore, mutant mice had normal plasma AVP levels and a normal AVP secretory response, but had significantly lower adrenocortical responsiveness to adrenocorticotropic hormone. Taken together, these results indicate that the V1a receptor plays an important role in normal resting arterial BP regulation mainly by its regulation of circulating blood volume and baroreflex sensitivity.

Adrenal Cortex↗
PubMed2006

Ablation of PDK1 in pancreatic beta cells induces diabetes as a result of loss of beta cell mass.

The total mass of islets of Langerhans is reduced in individuals with type 2 diabetes, possibly contributing to the pathogenesis of this condition. Although the regulation of islet mass is complex, recent studies have suggested the importance of a signaling pathway that includes the insulin or insulin-like growth factor-1 receptors, insulin receptor substrate and phosphatidylinositol (PI) 3-kinase. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a serine-threonine kinase that mediates signaling downstream of PI 3-kinase. Here we show that mice that lack PDK1 specifically in pancreatic beta cells (betaPdk1-/- mice) develop progressive hyperglycemia as a result of a loss of islet mass. The mice show reductions in islet density as well as in the number and size of cells. Haploinsufficiency of the gene for the transcription factor Foxo1 resulted in a marked increase in the number, but not the size, of cells and resulted in the restoration of glucose homeostasis in betaPdk1-/- mice. These results suggest that PDK1 is important in maintenance of pancreatic cell mass and glucose homeostasis.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed2006

Reliability and validity of the Japanese-language version of the physical performance test (PPT) battery in chronic pain patients.

PURPOSE: To prepare a Japanese-language version of the Physical Performance Test (PPT) Battery and assess its reliability and validity. METHOD: Activity limitations by pain were evaluated by means of the Japanese-language version of the PPT Battery in 82 patients with chronic pain in the limbs and trunk. Two self-report questionnaires, one related to sensory evaluation of pain, and the other related to affective evaluation of pain, and the Functional Independence Measure (FIM), which evaluates activities of daily living, were simultaneously administered to the subjects. RESULTS: The results for reliability showed that the ICC values for inter-rater reliability and intra-rater reliability were 0.91 or more for every item. The results for validity showed significant associations between the scores for all of the items on the Japanese-language version of the PPT Battery and the total scores on the FIM (p < 0.01). Significant associations were found between 5 of the 8 items on the Japanese-language version of the PPT Battery and affective state due to the pain. CONCLUSIONS: The Japanese-language version of the PPT Battery was shown to possess adequate reliability and validity as a scale for evaluating the activity limitations of patients with chronic limb or trunk pain. The results also suggested that it might be possible to improve the activity limitations of patients with chronic pain by improving their affective state in response to the pain.

Activities of Daily Living↗
PubMed2006

Synchronization and maintenance of timekeeping in suprachiasmatic circadian clock cells by neuropeptidergic signaling.

Circadian timekeeping in mammals is driven by transcriptional/posttranslational feedback loops that are active within both peripheral tissues and the circadian pacemaker of the suprachiasmatic nuclei (SCN). Spontaneous synchronization of these molecular loops between SCN neurons is a primary requirement of its pacemaker role and distinguishes it from peripheral tissues, which require extrinsic, SCN-dependent cues to impose cellular synchrony. Vasoactive intestinal polypeptide (VIP) is an intrinsic SCN factor implicated in acute activation and electrical synchronization of SCN neurons and coordination of behavioral rhythms. Using real-time imaging of cellular circadian gene expression across entire SCN slice cultures, we show for the first time that the Vipr2 gene encoding the VPAC2 receptor for VIP is necessary both to maintain molecular timekeeping within individual SCN neurons and to synchronize molecular timekeeping between SCN neurons embedded within intact, organotypical circuits. Moreover, we demonstrate that both depolarization and a second SCN neuropeptide, gastrin-releasing peptide (GRP), can acutely enhance and synchronize molecular timekeeping in Vipr2-/- SCN neurons. Nevertheless, transiently activated and synchronized Vipr2-/- cells cannot sustain synchrony in the absence of VIP-ergic signaling. Hence, neuropeptidergic interneuronal signaling confers a canonical property upon the SCN: spontaneous synchronization of the intracellular molecular clockworks of individual neurons.

Animals↗
PubMed2006

Real-time imaging of the somite segmentation clock: revelation of unstable oscillators in the individual presomitic mesoderm cells.

Notch signaling components such as the basic helix-loop-helix gene Hes1 are cyclically expressed by negative feedback in the presomitic mesoderm (PSM) and constitute the somite segmentation clock. Because Hes1 oscillation occurs in many cell types, this clock may regulate the timing in many biological systems. Although the Hes1 oscillator is stable in the PSM, it damps rapidly in other cells, suggesting that the oscillators in the former and the latter could be intrinsically different. Here, we have established the real-time bioluminescence imaging system of Hes1 expression and found that, although Hes1 oscillation is robust and stable in the PSM, it is unstable in the individual dissociated PSM cells, as in fibroblasts. Thus, the Hes1 oscillators in the individual PSM cells and fibroblasts are intrinsically similar, and these results, together with mathematical simulation, suggest that cell-cell communication is essential not only for synchronization but also for stabilization of cellular oscillators.

Animals↗
PubMed2006

Structural changes and cell properties of human ovarian surface epithelium in ovarian pathophysiology.

The surface epithelial cells of the ovary, which are modified peritoneal cells, form a single, focally pseudostratified layer. The Müllerian ducts differentiate after invagination of the coelomic mesothelium over the gonadal ridges during the 6th week of embryonic life. On the basis of the embryologically putative Müllerian potential of this epithelium, endometriosis can be explained by coelomic metaplasia from the peritoneum, including ovarian surface epithelium. Some pelvic endometriosis specimens have shown that epithelial cells on the ovary or pelvis are serially changed to endometriotic gland cells. Immunohistochemistry as well as scanning electron microscopy also reinforce the light-microscopical findings. A three-dimensional culture system demonstrated that human ovarian surface epithelial cells exhibited a glandular-stromal structure when they were cocultured with endometrial stromal cells in an estrogen-rich environment. Ovarian carcinomas in the epithelial-stromal category are thought to arise from the surface epithelium and its inclusions. The ovarian surface epithelium is physiologically involved in follicular rupture, oocyte release, and the subsequent repair of follicle wall during reproductive age. Simultaneously, ovulation may cause a loss of integrity of the surface epithelium, followed by accumulation of multiple mutations. The cortical invagination, surface stromal proliferation, and Müllerian differentiation of these cells are likely not to be an early step in the cancer development. However, the inclusion cysts are closely related with carcinogenesis because they are significantly more common in ovaries contralateral to those containing epithelial cancers than in control ovaries. As an in vitro study, ovarian carcinoma cell lines were established from simian virus 40 large T antigen-transformed human surface epithelial cells of the ovary. Further investigations of these cell lines may lead to insights into the preneoplastic and early stages of carcinomas. To clarify the pathogenesis of endometriosis and epithelial ovarian cancer, specifically designed studies of ovarian surface epithelium are required.

Endometriosis↗
PubMed2006

Role of hepatic STAT3 in brain-insulin action on hepatic glucose production.

STAT3 regulates glucose homeostasis by suppressing the expression of gluconeogenic genes in the liver. The mechanism by which hepatic STAT3 is regulated by nutritional or hormonal status has remained unknown, however. Here, we show that an increase in the plasma insulin concentration, achieved either by glucose administration or by intravenous insulin infusion, stimulates tyrosine phosphorylation of STAT3 in the liver. This effect of insulin was mediated by the hormone's effects in the brain, and the increase in hepatic IL-6 induced by the brain-insulin action is essential for the activation of STAT3. The inhibition of hepatic glucose production and of expression of gluconeogenic genes induced by intracerebral ventricular insulin infusion was impaired in mice with liver-specific STAT3 deficiency or in mice with IL-6 deficiency. These results thus indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in the brain, leading to the suppression of hepatic glucose production.

Animals↗
PubMed2006

Neonatal estrogenic exposure suppresses PTEN-related endometrial carcinogenesis in recombinant mice.

Human endometrial carcinomas, as well as complex atypical hyperplasias (CAH), are estrogen related and frequently have mutations in the PTEN gene. However, the mutual contribution of estrogen and PTEN mutations to endometrial carcinogenesis in vivo is unknown. To address this issue, we investigated whether neonatal estrogenic treatments augment the incidence of CAH and carcinomas in murine PTEN (mPTEN) heterozygous (+/-) mutant mice, an animal model for endometrial carcinoma. Low doses of diethylstilbestrol (1 ng/g/day), genistein (50 microg/g/day) in phytoestrogens, estriol (E(3)) (4 microg/g/day), and vehicle (ethanol and corn oil) were administered subcutaneously daily to neonatal pups from the 1st to 5th day after birth. At 52 weeks of age, the morphological changes in the endometrium, and uterine expression of Hoxa 10 and Hoxa 11, were evaluated. These Hoxa genes are abdominal B-type homeobox genes, which normally regulate differentiation of the Müllerian duct. The incidence of CAH and adenocarcinomas of the endometrium was significantly decreased by the neonatal estrogenic treatments in the mPTEN+/- mice. Coincidentally, all treatments significantly decreased the stromal cell density, and CAH and adenocarcinomas rarely developed in the epithelium adjacent to the affected endometrial stroma. Moreover, the uterine expression of Hoxa 10 in mice with neonatal genistein and E(3) treatments, and that of Hoxa 11 in mice with all treatments, was significantly lower when compared with vehicle alone. Taken together, neonatal estrogenic exposure induced stromal atrophy and/or hyalinization accompanied by repressed expression of Hoxa 10 and Hoxa 11, and exerted an inhibitory effect on PTEN-related tumorigenesis. These findings provide new insight into the interaction between endometrial epithelium and stroma in endometrial carcinogenesis in vivo.

Adenocarcinoma↗
PubMed2006

Does mPER2 protein oscillate without its coding mRNA cycling?: post-transcriptional regulation by cell clock.

Does the mammalian oscillatory protein mPER2 show the rhythm without its coding mRNA cycling? Here we answer this question by inserting a single copy of exogenous mPer2 gene to a NIH3T3 fibroblasts cell line, using Flp-In system. We generated the stable cell lines which constantly express mRNAs coding either N-terminal FLAG-tagged full length mPER2 (FLAG-mPER2(full)) or its C-terminal deleted form (FLAG-mPER2(1-1068)), which lacks the binding site to mCRY proteins, under the control of human EF-1alpha promoter. Although serum shock induced the rhythm of endogenous clock machinery in these cell lines, it did not initiate the rhythm of exogenously inserted FLAG-mPer2 genes at the mRNA level. In contrast, FLAG-mPER2(full) proteins showed the rhythm without their coding mRNA cycling. Since cells expressing FLAG-mPER2(1-1068) also showed the rhythm of FLAG-mPER2(1-1068) proteins, the direct binding of mCRY and mPER2 seems not necessary for this protein oscillation. This system clearly demonstrates that the intracellular endogenous clock system has an ability to modify the mPer2 gene post-transcriptionally to make mPER2 proteins oscillate without its coding mRNA cycling.

Animals↗
PubMed2006

Psychological impact of verbal abuse and violence by patients on nurses working in psychiatric departments.

The aim of this study was to assess the psychological impact of verbal abuse or violence by patients on nurses working in psychiatry departments and to identify factors related to their impact. Survey sheets were distributed to a total of 266 nurses working at two hospitals, and replies were obtained from 232 of them. Because three of them had less than 1 month of experience working in the psychiatry department and four of them failed to answer all the questions, valid replies were obtained from 225 nurses. Among the 225 whose replies were valid, 141 nurses who replied that they had experienced verbal abuse or violence that left an impression on them remained as the subjects of the final analysis. The Impact of Event Scale-Revised (IES-R) was used to evaluate psychological impact. Of the nurses who had been exposed to verbal abuse or violence that left an impression, 21% had scores that exceeded the IES-R cut-off point (24/25), and low satisfaction with family support, and neuroticism on the Eysenck Personality Questionnaire-Revised were shown to have contributed to the psychological impact. Nurses working in psychiatry departments were shown to experience a severe psychological impact when exposed to verbal abuse or violence. These results suggest the need for mental care approaches for nurses working in psychiatry departments.

Adaptation, Psychological↗
PubMed2006

Functional evolution of the photolyase/cryptochrome protein family: importance of the C terminus of mammalian CRY1 for circadian core oscillator performance.

Cryptochromes (CRYs) are composed of a core domain with structural similarity to photolyase and a distinguishing C-terminal extension. While plant and fly CRYs act as circadian photoreceptors, using the C terminus for light signaling, mammalian CRY1 and CRY2 are integral components of the circadian oscillator. However, the function of their C terminus remains to be resolved. Here, we show that the C-terminal extension of mCRY1 harbors a nuclear localization signal and a putative coiled-coil domain that drive nuclear localization via two independent mechanisms and shift the equilibrium of shuttling mammalian CRY1 (mCRY1)/mammalian PER2 (mPER2) complexes towards the nucleus. Importantly, deletion of the complete C terminus prevents mCRY1 from repressing CLOCK/BMAL1-mediated transcription, whereas a plant photolyase gains this key clock function upon fusion to the last 100 amino acids of the mCRY1 core and its C terminus. Thus, the acquirement of different (species-specific) C termini during evolution not only functionally separated cryptochromes from photolyase but also caused diversity within the cryptochrome family.

ARNTL Transcription Factors↗
PubMed2006

Circadian intraocular pressure rhythm is generated by clock genes.

PURPOSE: The present study in a mouse model was undertaken to reveal the role of the circadian clock genes Cry1 and Cry2 in generation of 24-hour intraocular pressure (IOP) rhythm. METHODS: IOP was measured at eight time points daily (circadian time [CT] 0, 3, 6, 9, 12, 15, 18, and 21 hours), using a microneedle method in four groups of C57BL/6J mice (groups 1 and 3, wild-type; groups 2 and 4, Cry-deficient [Cry1-/-Cry2-/-]). During the IOP measurements, mice in groups 1 and 2 were maintained in a 12-hour light-dark cycle (LD), whereas mice in groups 3 and 4 were kept in a constant darkness (DD) that started 24 to 48 hours before the measurements. Circadian IOP variations in each group were evaluated by one-way analysis of variance (ANOVA) and Scheffé tests. RESULTS: In wild-type mice living in LD conditions, pressures measured in the light phase were significantly lower than those in the dark phase. This daily rhythm was maintained under DD conditions with low pressure in the subjective day and high pressure in the subjective night. In contrast, Cry-deficient mice did not show significant circadian changes in IOP, regardless of environmental light conditions. CONCLUSIONS: These findings demonstrate that clock oscillatory mechanisms requiring the activity of core clock genes are essential for the generation of a circadian rhythm of intraocular pressure.

Animals↗
PubMed2006

Activation of follistatin promoter by GnRH in LbetaT2 gonadotroph cells.

Follistatin (FS) is produced and secreted from gonadotroph cells in pituitary gland as well as granulosa cells in the ovary. In the present study, we found that the FS promoter is activated by GnRH in the gonadotroph cell line, LbetaT2. Therefore, we examined the signal transduction pathways involved in the mechanism. The activation of the FS promoter by GnRH was inhibited by calphostin C, a protein kinase C inhibitor, and U0126, a MAP kinase kinase (MEK) inhibitor. Phosphorylation by protein kinase C of myristoylated alanine-rich C kinase substrate (MARCKS) in LbetaT2 cells was observed after 3-min treatment with GnRH and declined after 30 min. The subsequent activation of MAP kinase was also transient, and down-regulation of protein kinase C completely inhibited the MAP kinase activation by GnRH, suggesting that the transient activation of protein kinase C led to the transient activation of MAP kinase. Although phorbol 12-myristate 13-acetate treatment increased phosphorylation of MARCKS and activated MAP kinase, it did not activate the FS promoter. Genistein, a tyrosine kinase inhibitor, completely inhibited the GnRH-induced activation of the FS promoter, while no inhibition of the MAP kinase pathway was observed. These results suggest that the activations of both the protein kinase C and tyrosine kinase pathways are necessary for the activation of the FS promoter in gonadotroph cells.

Animals↗
PubMed2005

Chronic treatment with prednisolone represses the circadian oscillation of clock gene expression in mouse peripheral tissues.

Although altered homeostatic regulation, including disturbance of 24-h rhythms, is often observed in the patients undergoing glucocorticoid therapy, the mechanisms underlying the disturbance remains poorly understood. We report here that chronic treatment with a synthetic glucocorticoid, prednisolone (PSL), can cause alteration of circadian clock function at molecular level. Treatment of cultured hepatic cells (HepG2) with PSL induced expression of Period1 (Per1), and the PSL treatment also attenuated the serum-induced oscillations in the expression of Period2 (Per2), Rev-erbalpha, and Bmal1 mRNA in HepG2 cells. Because the attenuation of clock gene oscillations was blocked by pretreating the cells with a Per1 antisense phosphothioate oligodeoxynucleotide, the extensive expression of Per1 induced by PSL may have resulted in the reduced amplitude of other clock gene oscillations. Continuous administration of PSL into mice constitutively increased the Per1 mRNA levels in liver and skeletal muscle, which seems to attenuate the oscillation in the expressions of Per2, Rev-erbalpha, and Bmal1. However, a single daily administration of PSL at the time of day corresponding to acrophase of endogenous glucocorticoid levels had little effect on the rhythmic expression of clock genes. These results suggest a possible pharmacological action by PSL on the core circadian oscillation mechanism and indicate the possibility that the alteration of clock function induced by PSL can be avoided by optimizing the dosing schedule.

ARNTL Transcription Factors↗