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Biomedical subjects

H Sakaguchi

Publications and source records attributed to H Sakaguchi.

At least 109 records · Page 6Linked to original sources

Auditory-vocal cholinergic pathway in the songbird brain.

Male zebra finches learn to imitate a tutor's song through auditory and motor learning. The two main song control nuclei in the zebra finch forebrain, the higher vocal center (HVC) and the robust nucleus of the archistriatum (RA), receive cholinergic innervation from the ventral paleostriatum (VP) of the basal forebrain which may play a key role in song learning. By injecting neuroanatomical tracers, we found a topographically segregated pathway from nucleus ovoidalis (Ov) to VP that in turn projects in a topographic fashion to HVC and RA. Ov is a major relay in the main ascending auditory pathway. The results suggest that the cholinergic neurons in the VP responsible for song learning are regulated by auditory information from the Ov.

Animals↗

Sex differences in the vocal motor pathway of the zebra finch revealed by real-time optical imaging technique.

Male zebra finches sing, whereas female zebra finches do not. To elucidate the neural mechanisms underlying sexual dimorphism in song behavior, the spatio-temporal properties of neural activity in the vocal motor pathway of the zebra finch were examined in sliced brain preparations using a real-time optical recording technique. Electrical stimulation to higher vocal center (HVC) fibers induced within 20 ms neural activities in the robust nucleus of the archistriatum (RA) of both male and female finches, although the amplitude was smaller and the latency was greater in females than in males. Bicuculline, a GABA(A) receptor antagonist, induced a robust activity in female RA, but had little effect in males. This suggests that neural connections from HVC to RA in female zebra finches are inhibited by GABAergic inputs. The results provide first evidence that an inhibitory neurotransmitter is involved in the sex difference in the motor vocal pathway of song birds.

Animals↗

Progestins suppress estrogen-induced expression of vascular endothelial growth factor (VEGF) subtypes in uterine endometrial cancer cells.

Vascular endothelial growth factor (VEGF) contributes to the early advancement of uterine endometrial cancers that conserve hormone dependency via angiogenic activity. This process prompted us to study sex steroidal suppression of VEGF expression in Ishikawa cells (a line of well-differentiated uterine endometrial cancer cells). Estrogen transiently induced VEGF subtype (VEGF165 and VEGF121) secretion from Ishikawa cells. Progestins (progesterone, medroxyprogesterone acetate (MPA) and 17 alpha-hydroxyprogesterone) suppressed the estrogen-induced events. In conclusion, progestins could suppress VEGF-related angiogenic potential, which contributes to tumor growth in the early stage of uterine endometrial cancers that conserve estrogen dependency.

17-alpha-Hydroxyprogesterone↗

Clinical implication of expression of platelet-derived endothelial cell growth factor (PD-ECGF) in metastatic lesions of uterine cervical cancers.

The platelet-derived endothelial cell growth factor (PD-ECGF) level was significantly (P < 0.05) increased in 8 of 40 metastatic lymph node lesions of uterine cervical cancers. The prognosis of the eight patients with high PD-ECGF (>10,000 pg/mg protein) in metastatic lymph node lesions was extremely poor. On the other hand, the 24-month survival rate of the 32 patients with low PD-ECGF (<10,000 pg/mg protein) in metastatic lymph node lesions was 75%. This indicates that PD-ECGF may contribute to the advancement of metastatic lesions, and that the PD-ECGF level in metastatic lesions may be a prognostic indicator.

Adult↗

Song-induced phosphorylation of cAMP response element-binding protein in the songbird brain.

We have investigated the participation of cAMP response element-binding protein (CREB) in the response of the songbird brain to a natural auditory stimulus, a conspecific song. The cells in the two song control nuclei, the higher vocal center (HVC) and area X of zebra finches (Taeniopygia guttata), were intensely stained with an anti-CREB monoclonal antibody. Double-labeling studies showed that CREB immunoreactivity was detected only in area X-projecting neurons in the HVC. The cloned CREB cDNA from zebra finches (zCREB) is highly homologous to mammalian delta CREB. Phosphorylation of zCREB at Ser119 in area X-projecting HVC neurons was induced by hearing tape-recorded conspecific songs of zebra finches, but not by birdsongs of another species or white noise. These results raise the possibility that zCREB plays a crucial role in the sensory process of song learning.

Amino Acid Sequence↗

Auditory-vocal cholinergic pathway in zebra finch brain.

The two main song control nuclei in the zebra finch forebrain, the higher vocal center (HVC) and the robust nucleus of the archistriatum (RA), receive cholinergic innervation from the ventral paleostriatum (VP) of the basal forebrain which may play a key role in song learning. By injecting two kinds of neuroanatomical tracers, we found that a topographically segregated pathway from nucleus ovoidalis (Ov) and nucleus dorsomedialis posterior thalami (DMP) to VP and further to RA and HVC. Ov is known as a major relay in the main ascending auditory pathway. The results suggest that cholinergic neurons in the VP which are responsible for song learning are regulated by auditory information from the Ov.

Acetylcholine↗

Axillofemoral bypass for recurrent atypical coarctation of the thoracic aorta. Woman in childbearing age.

Various surgical techniques for recurrent atypical coarctation have been described, and extra-anatomic bypass with a thoracotomy or a sternotomy approach has been widely recommended. We report a case where axillofemoral bypass has been used to treat a 28-year-old woman with recurrent atypical coarctation. Ordinarily, she had not suffered greatly from hypertension, but she experienced repeated miscarriages most probably owing to uncontrolled hypertension over 200 mmHg during pregnancy. We chose an axillofemoral bypass for extra-anatomic bypass to manage intractable hypertension during pregnancy. Postoperatively, her hemodynamics improved substantially, particularly during pregnancy, and two children were successfully delivered. The patient remains in excellent condition 74 months after operation. We suggest that an axillofemoral bypass will become an option among surgical techniques for recurrent coarctation under individual circumstances.

Adult↗

Expression of size-polymorphic androgen receptor (AR) gene in ovarian endometriosis according to the number of cytosine, adenine, and guanine (CAG) repeats in AR alleles.

An increase in androgen receptor (AR) caused by estrogen is recognized as one of the biological phenomena related to estrogen-induced growth in uterine endometrium. The A/B region of AR gene in X chromosome involves the cytosine, adenine, and guanine (CAG) repeats. Random X chromosome inactivation with AR alleles in individual cells occurs in females. Therefore, approximately either paternal or maternal single dominant polymorphic AR mRNA must be expressed in neoplastic tissue originated from monoclone. This prompted us to determine deviated number of CAG repeats in AR mRNA to understand clonality in ovarian endometriosis. In all cases of heterozygous AR alleles, although paternal and maternal AR mRNAs from normal eutopic uterine endometrium were consistently expressed as AR alleles, either paternal or maternal single dominant AR mRNA expression was found in an individual ovarian endometrioma. Therefore, an individual ovarian endometrioma might be formed from an independent monoclonal ovarian endometriotic endometrial cell after inactivation of either AR allele in X chromosome.

Adenine↗

Expression of platelet-derived endothelial cell growth factor (PD-ECGF) and its mRNA in uterine cervical cancers.

Angiogenesis contributes to the growth and secondary spreading of solid tumours. Platelet-derived endothelial cell growth factor (PD-ECGF) is identified as such an angiogenic factor. In the present study, the prognosis of the patients with high PD-ECGF uterine cervical cancers was worse than those with low PD-ECGF cancers, and PD-ECGF expression correlated with cellular proliferation and with vascular density and venous invasion in uterine cervical cancers. Therefore, PD-ECGF might contribute to the growth of uterine cervical cancers via angiogenesis related to vascular spreading. Furthermore, PD-ECGF and its mRNA had a wide range and were highly expressed in uterine cervical cancers, especially squamous cell carcinoma, regardless of clinical stage. Therefore, PD-ECGF in uterine cervical cancers might play a role of basic angiogenesis in all processes of advancing of uterine cervical cancers. This indicates that 5'-deoxy-5-fluorouridine might be highly effective in squamous cell carcinoma of the cervix, which possesses a high activity of thymidine phosphorylase to convert 5'-deoxy-5-fluorouridine to 5-fluorouracil, and that some angiogenic inhibitors of new capillary formation might be effective in the inhibition of tumour growth and spreading associated with angiogenesis.

Adult↗

Expression of vascular endothelial growth factor (VEGF) and its mRNA in uterine cervical cancers.

To know the potential of growth, invasion and metastasis of uterine cervical cancer associated with neovascularization, localization of vascular endothelial growth factor (VEGF) and microvessel density in tumours were determined by immunohistochemical staining, the levels of VEGF subtypes were determined by Western blot analysis and by a sandwich enzyme immunoassay, and the levels of VEGF subtype mRNAs were determined by reverse transcription polymerase chain reaction (RT-PCR)-Southern blot analysis in uterine cervical cancers. The relation between VEGF subtype expressions and microvessel density, histological types and clinical stages of uterine cervical cancers was analysed. The expression of VEGF was seen dominantly in the cancer cells, and correlated with microvessel density in uterine cervical cancers. Among the four subtypes of VEGF, the populations of VEGF165 and VEGF121 were dominant in normal uterine cervices and uterine cervical cancers. The levels of VEGF and VEGF165 and VEGF121 mRNAs were remarkably higher in some stage II and III/IV adenocarcinomas of the cervix than in other cases, including normal cervices. Therefore, the elevation of VEGF165 and VEGF121 might contribute to the relatively late advancing via angiogenic activity in some adenocarcinomas of the cervix.

Adult↗

Effects of cicletanine on the progression of renal failure in 5/6 nephrectomized hypertensive rats.

1. The effect of cicletanine, a novel antihypertensive agent with natriuretic activity, on blood pressure and progression of renal failure of 5/6 nephrectomized spontaneously hypertensive rats with salt loading was examined. 2. All nephrectomized rats were randomly assigned to one of four groups and their diet was changed from a normal- to a high-salt (5.5% NaCl) diet for the next 10 weeks. Either 10 or 50 mg/kg per day cicletanine (low- and high-dose cicletanine, respectively) or 10 mg/kg per day trichlormethiazide were administered to rats during this period once a day. During the experimental period, urine volume, urinary excretion of sodium, protein, prostaglandin (PG) E2 and 6-keto-PGF1 alpha and systolic blood pressure (SBP) were measured every 2 weeks. 3. Systolic blood pressure was significantly reduced by the administration of trichlormethiazide and the higher dose of cicletanine, but not by the lower dose of cicletanine. 4. In contrast with changes to SBP, levels of serum creatinine in rats treated with both doses of cicletanine were significantly lower than in controls (0.57 +/- 0.12, 0.78 +/- 0.12 and 1.68 +/- 0.26 mg/dL for high- and low-dose cicletanine and control, respectively). 5. Urinary excretion of both PGE2 and 6-keto-PGF1 alpha were significantly increased in groups treated with high and low doses of cicletanine compared with control. In rats treated with trichlormethiazide, PGE2 and 6-keto-PGF1 alpha levels were significantly decreased compared with control. 6. In contrast with changes in SBP, marked glomerular sclerosis with hyalinosis found in the control group was not ameliorated by trichlormethiazide treatment. These changes were not observed in rats treated with low- and high-dose cicletanine, particularly those treated with the higher dose of cicletanine. 7. These data suggest that administration of cicletanine has a beneficial protective effect regarding the progression of renal failure, regardless of the level of blood pressure, through a direct and/or indirect action on the glomerulus.

6-Ketoprostaglandin F1 alpha↗

Expression of oestrogen receptor-alpha and -beta in ovarian endometriomata.

The contribution of oestrogen receptor (ER) isoforms, ER-alpha and ER-beta, in oestrogen-dependent development and growth of ovarian endometriomata, is unknown. Therefore, we examined the expression of ER-alpha and ER-beta in ovarian endometriomata and normal uterine endometrium. ER-alpha and ER-beta were shown to be dominantly expressed in the nuclei of the epithelial lining cells of ovarian endometrioma and of the glandular cells of normal uterine endometrium. ER-beta was expressed at a much lower level than ER-alpha in the glandular cells of normal uterine endometrium, while ER-beta was expressed at a slightly lower level than ER-alpha in the epithelial lining cells of ovarian endometrioma. In normal uterine endometrium, ER-beta mRNA was expressed at a much lower level than ER-alpha mRNA, and the expression pattern of ER-beta mRNA during the menstrual cycle was similar to that of ER-alpha mRNA. On the other hand, ER-beta mRNA expression was significantly higher and over a much greater range in ovarian endometriomata (P < 0.05) than in normal uterine endometrium during the menstrual cycle, while ER-alpha mRNA expression was relatively lower and more random. Therefore, in ovarian endometriomata, oestrogen action via ER-alpha cascades seems to be partially damaged, as the expression of ER-alpha mRNA does not respond to endocrinological alterations during the menstrual cycle, while the relative over-expression of ER-beta might be related to a unique oestrogen-dependent growth and spreading of ovarian endometriomata.

Adult↗

Coupled modified baker's transformations for the Ising model.

An invertible coupled map lattice is proposed for the Ising model. Each elemental map is a modified baker's transformation, which is a two-dimensional map of X and Y. The time evolution of the spin variable is memorized in the binary representation of the Y variable. The temporal entropy and time correlation of the spin variable are calculated from the snapshot configuration of the Y variables.

Journal Article↗

Angiogenesis in endometriosis and angiogenic factors.

Among angiogenic factors, VEGF secreted from activated macrophages under the influence of ovarian steroids, IL-8 expressed in endometrial stromal cells, and basic FGF expressed in endometriotic tissue and PD-ECGF expressed in lining epithelial cells independently of the sex steroidal milieu might contribute to the characteristic advancement of angiogenic lesions in endometriosis in individual manners. Copyrightz1999S.KargerAG,Basel

Adult↗

Progestin regulation in tumor growth of female genital tract cancers.

The irregular response to progestins directly in tumor growth might be caused by dominant negative progesterone receptor (PR) mutants and the damage to PR-A expression. Progestin treatment as an anti-angiogenic therapy would be less effective in the PR-mutated tumors. Therefore, various anti-angiogenic inhibitors must be used in progestin-refractory and progestin-dependent tumors.

Endothelial Growth Factors↗

Expression of platelet-derived endothelial cell growth factor (PD-ECGF) related to angiogenesis in ovarian endometriosis.

Platelet-derived endothelial cell growth factor (PD-ECGF) is expressed in the lining epithelial cells of ovarian endometriomas, and in interstitial cells of the subepithelial area with angiogenesis. The expression of PD-ECGF persists in endometriotic endometrium during the menstrual cycle. This might suggest that PD-ECGF contributes to the growth of ovarian endometriomas via subepithelial angiogenesis independently of the sex steroidal milieu.

Adult↗

Evaluation of cases with silicosis using the parameters related to Fas-mediated apoptosis.

To establish a new clinical index for immunological abnormalities occurring in silicosis, several clinical parameters related to Fas-mediated apoptosis; i.e., membrane Fas expression on peripheral blood lymphocytes (mFas), serum soluble Fas levels (sFas), serum soluble Fas ligand levels (sFasL), and soluble/membrane Fas mRNA expression ratios (s/mFas ExR) in peripheral blood mononuclear cells (PBMC) were investigated. Fifty-eight silicosis patients with no clinical symptoms of autoimmune diseases were the subjects of this study. Factor analysis was performed using 12 clinical parameters including four parameters related to Fas-mediated apoptosis. Two common factors were identified. Factor 1 which consisted of the following parameters; duration of exposure, symptomatic dyspnea, PO2, PCO2, and A-aDO2, should be designated as the respiratory factor for cases with silicosis. The parameters of factor 2 were serum IgG, sFas with high factor loading, titer of ANA, sFasL, and s/mFas ExR. These parameters of factor 2 are indicative of the immunological disorders occurring in silicosis cases. Some cases exhibited abnormalities in parameters of factor 2 but not factor 1. The factor analysis clearly demonstrated that the parameters related to Fas-mediated apoptosis should be the most beneficial for predicting the pre-clinical status of complicated autoimmune diseases in silicosis.

Aged↗