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Biomedical subjects

H Sasano

Publications and source records attributed to H Sasano.

At least 37 records · Page 2Linked to original sources
PubMed2003

Isocapnic hyperpnoea accelerates recovery from isoflurane anaesthesia.

BACKGROUND: Hyperventilation should speed up elimination of volatile anaesthetic agents from the body, but hyperventilation usually results in hypocapnia. We compared recovery from isoflurane anaesthesia in patients allowed to recover with assisted spontaneous ventilation (control) and those treated with isocapnic hyperpnoea. METHODS: Fourteen patients were studied after approximately 1 h of anaesthesia with isoflurane. Control patients were allowed to recover in the routine way. Isocapnic hyperpnoea patients received 2-3 times their intraoperative ventilation using a system to maintain end tidal PCO(2) at 45-50 mm Hg. We measured time to removal of the airway and rate of change of bispectral index (BIS) during recovery. RESULTS: With isocapnic hyperpnoea, the time to removal of the airway was markedly less (median and interquartile range values of 3.6 (2.7-3.7) vs 12.1 (6.8-17.2) min, P<0.001); mean (SD) BIS slopes during recovery were 11.8 (4.4) vs 4.3 (2.7) min(-1) (P<0.01) for isocapnic hyperpnoea and control groups, respectively. Isocapnic hyperpnoea was easily applied in the operating room. CONCLUSIONS: Isocapnic hyperpnoea at the end of surgery results in shorter and less variable time to removal of the airway after anaesthesia with isoflurane and nitrous oxide.

Adult↗
PubMed2001

EBAG9/RCAS1 in human breast carcinoma: a possible factor in endocrine-immune interactions.

EBAG9 has been recently identified as an oestrogen responsive gene in MCF-7 human breast carcinoma cells. EBAG9 is identical to RCAS1, a cancer cell surface antigen possibly involved in immune escape. In this study, we examined the expression of EBAG9/RCAS1 in human breast carcinomas using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). EBAG9 immunoreactivity was also associated with various clinicopathological parameters, including intratumoural infiltration of inflammatory cells, to examine the biological significance of EBAG9 in human breast carcinomas. EBAG9 immunoreactivity was detected in the entire surface and cytoplasm of carcinoma cells in 82 out of 91 invasive ductal carcinomas (90.1%). In non-neoplastic mammary glands, EBAG9 immunoreactivity was weakly present on the luminal surface of epithelial cells. Results from RT-PCR (n = 7) were consistent with those of immunohistochemistry. EBAG9 immunoreactivity was significantly associated with estrogen receptor (ER) alpha labelling index (P = 0.0081), and inversely associated with the degree of intratumoural infiltration of mononuclear cells (P = 0.0020), or CD3(+) T lymphocytes (P = 0.0025). This study suggests that EBAG9 is produced via ER in carcinoma cells and inhibits the intratumoural infiltration of T lymphocytes in the context of a possible endocrine-immune interaction in human breast carcinomas.

Adult↗
PubMed2001

Role of urotensin II in patients on dialysis.

Urotensin II is a potent vasoconstrictor, which also has some vasodilatory properties. We investigated its expression in various tissues and in the plasma of patients with renal dysfunction. Plasma concentrations of urotensin II-like immunoreactivity were 2-fold higher in patients not on dialysis and 3-fold higher in those on haemodialysis thanin healthy individuals. Messenger RNA encoding theurotensin II precursor and the urotensin II receptor precursor were expressed in various human tissues. The peptidemight act as an important regulator in the cardiovascularand renal systems. Urotensin II antagonists could, therefore, be useful in the treatment of diseases affecting theseorgans.

Adult↗
PubMed2001

Spatial and topological distribution of progesterone receptor A and B isoforms during human development.

Progesterone receptor (PR) is a member of the nuclear receptor superfamily. To date, two isoforms of PR have been identified, PR-A and PR-B. In progesterone responsive tissues, the relative ratio of PR-A and PR-B is considered to contribute to the tissue-specific actions of progesterone. In this study, we examined the distribution of PR-A and PR-B in human fetal tissues ranging from 11 to 40 gestational weeks using immunohistochemistry and RT-PCR analysis. PR immunoreactivity was detected in a wide range of fetal tissues until 20 weeks of gestation, but gradually decreased towards the late gestational period. However, PR continued to remain positive throughout the gestational period in the interstitial cells of Cajal and endocrine tissues. PR-B was demonstrated as the predominant isoform in comparison to PR-A in all fetal tissues examined. These findings suggest that progesterone may be involved in the development of fetal organs throughout the gestational period.

Embryonic and Fetal Development↗
PubMed2001

Abnormal uterus with polycysts, accumulation of uterine prostaglandins, and reduced fertility in mice heterozygous for acyl-CoA synthetase 4 deficiency.

Arachidonate released by various stimuli is rapidly reesterified into membrane phospholipids initiated by acyl-CoA synthetase (ACS) and subsequent acyl-transfer reactions. ACS4 is an arachidonate-preferring enzyme abundant in steroidogenic tissues and postulated to modulate eicosanoid production. Female mice heterozygous for ACS4 deficiency become pregnant less frequently and produce small litters with extremely low transmission of the disrupted alleles. Striking morphological changes, including extremely enlarged uteri and lumina filled with numerous proliferative cysts of various sizes, were detected in ACS4+/- females. Furthermore, marked accumulation of prostaglandins was seen in the uterus of the heterozygous females. These results indicate that ACS4 modulates female fertility and uterine prostaglandin production.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

Distribution of various calcium channel alpha(1) subunits in murine DRG neurons and antinociceptive effect of omega-conotoxin SVIB in mice.

Immunohistological study revealed the differential localization of subtypes of voltage-dependent calcium channels in the dorsal root ganglion neurons. Intrathecal injection of omega-conotoxin SVIB, an analogue of omega-conotoxin GVIA, which acts on N-type voltage-dependent calcium channels, significantly shortened the licking time in the late phase of a formalin test.

Animals↗
PubMed2001

Temporal and spatial distribution of corticosteroidogenic enzymes immunoreactivity in developing human adrenal.

Steroid hormones secreted by fetal adrenocortical cells are considered to be a requirement for a fetus to maintain intrauterine life, but, to date, the regulation of steroid hormone secretion has not been studied in detail in the human fetal adrenal gland. In this study, we examined the immunolocalization of steroidogenic enzymes and their local regulation, including adrenal 4-binding protein (Ad4BP or NR5A1), steroidogenic acute regulatory protein (StAR), P450 cholesterol side-chain cleavage (P450scc or CYP11A1), P450 17alpha-hydroxylase/17,20-lyase (P450c17 or CYP17), 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD), P450 21 hydroxylase (P450c21 or CYP21), dehydroepiandrosterone sulfotransferase (DHEA-ST), P450 oxidoreductase and cytochrome b5, in the human fetal adrenal gland (n=31) obtained from fetuses ranging in ages from 14 to 40 weeks of gestation. Ad4BP immunoreactivity was detected in all adrenocortical zones throughout gestation, suggesting that this nuclear protein is likely to be essential in the development of the human adrenal. Immunoreactivity for StAR, P450scc, P450c21, P450 oxidoreductase and cytochrome b5 was detected only in fetal and transitional zone between 14 and 22 weeks of gestation, but was detected in all three zones after 23 gestational weeks. 3beta-HSD immunoreactivity was not detected in any of the three cortical zones prior to 22 weeks of gestation, but became discernible in the transitional zone and definitive zone after 23 weeks. Immunoreactivity for P450c17 and DHEA-ST was detected in the transitional and fetal zones throughout gestation, but not in the definitive zone. These results suggest that the human adrenal cortex may produce dehydroepiandrosterone (DHEA) in the transitional and fetal zones throughout gestation, and cortisol in the transitional zone after the 23rd week of gestation.

Adrenal Cortex Hormones↗
PubMed2001

Tumor necrosis factor alpha and interleukin 11 secreted by malignant breast epithelial cells inhibit adipocyte differentiation by selectively down-regulating CCAAT/enhancer binding protein alpha and peroxisome proliferator-activated receptor gamma: mechanism of desmoplastic reaction.

The dense layer of fibroblasts that accumulate around malignant breast epithelial cells (i.e., desmoplastic reaction) arises from the breast adipose tissue and provides structural and biochemical support for breast cancer. We report herein a number of epithelial-stromal interactions responsible for desmoplastic reaction in breast cancer using cultured 3T3-L1 murine fibroblasts and human adipose fibroblasts, which can be activated with a mixture of hormones to differentiate to mature adipocytes. Adipocyte differentiation was inhibited by coculturing fibroblasts with various breast cancer cell lines (T47D, MCF-7, SSC202, SSC78, and SSC30) completely or by breast cancer cell conditioned media in a dose-dependent manner; on the other hand, adipocyte differentiation was not inhibited by coculturing with normal human primary mammary epithelial cell conditioned medium. This tumor effect was eliminated using neutralizing antibodies against tumor necrosis factor (TNF)-alpha or interleukin (IL)-11. TNF-alpha and IL-11 levels were 2.5-3 times higher in T47D conditioned medium compared with control medium, and TNF-alpha transcripts were detectable in T47D but not in 3T3-L1 cells in culture, indicating that the malignant epithelial cell is the major site of cytokine production. This was confirmed in vivo in mastectomy specimens, where immunoreactive TNF-alpha and IL-11 were readily detectable in malignant epithelial cells but not in the majority of the surrounding fibroblasts. Adipocyte differentiation is mediated by the expression of a cascade of adipogenic transcription factors, including CCAAT/enhancer binding protein (C/EBP)beta, C/EBPdelta, peroxisome proliferator-activated receptor (PPAR)gamma and C/EBPalpha. C/EBPalpha and PPARgamma are essential for this process. We demonstrated by Northern analysis that exposure of activated 3T3-L1 cells to T47D cell conditioned medium strikingly decreased the levels of PPARgamma and C/EBPalpha transcripts and increased the levels of C/EBPbeta and C/EBPdelta transcripts. In these 3T3-L1 cells, inhibition of differentiation was also confirmed by markedly suppressed levels of aP2 mRNA, which is an adipocyte-specific gene. These in vitro observations were confirmed in sections of human malignant breast tumors, where immunoreactive C/EBPalpha was readily detectable in adipose flbroblasts distant to the tumor but not in intratumoral fibroblasts. Treatment of 3T3-L1 cells with T47D cell conditioned medium or TNF-alpha changed neither the numbers of cells in G0-G1, S, and G2 phases nor the rate of [3H]thymidine incorporation, thus ruling out a proliferative effect of malignant cells on the surrounding fibroblasts. In summary, desmoplastic reaction primarily occurs via the action of cytokines (TNF-alpha and IL-11) secreted by the malignant epithelial cells to inhibit differentiation of adipose fibroblasts to mature adipocytes. This tumor-induced block in adipocyte differentiation is mediated by the selective inhibition of expression of the essential adipogenic transcription factors, i.e., PPARgamma and C/EBPalpha.

3T3 Cells↗
PubMed2001

Immunohistochemical distribution of 11beta-hydroxysteroid dehydrogenase in human eye.

11beta-hydroxysteroid dehydrogenase (11beta-HSD) regulates local actions of corticosteroids at glucocorticoid and mineralocorticoid receptors. Corticosteroids are thought to play important roles in ocular function. However, mechanisms of intraocular corticosteroid action are still unclear. Therefore, in this study, we examined the immunohistochemical localization of 11beta-HSD type 1 (11beta-HSD1), 11beta-HSD type 2 (11beta-HSD2), mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in human ocular tissues from patients (6 months to 78 years of age; n = 10) retrieved from surgical pathology files. Both 11beta-HSD2 and MR immunoreactivity was detected only in non-pigmented epithelium of the ciliary body, but was undetectable in cornea, lens, iris, retina, choroid and sclera, in all the cases examined. GR was detected in all cell types in the human eye. 11beta-HSD1 immunoreactivity was not detected in the human eye in this study. These results suggest that 11beta-HSD2 play an important role in human ocular mineralocorticoid action, such as the production of aqueous humor, in the ciliary body. The widespread expression of GR suggests that glucocorticoids may play an important role in the function and homeostasis of the human eye.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2001

Pan1b (17betaHSD11)-enzymatic activity and distribution in the lung.

We describe a new member of the 17beta-hydroxysteroid dehydrogenase group of enzymes. Human Pan1b displays greatest activity with 5alpha-androstan-3alpha,17beta-diol (3alpha-Diol) as substrate, suggesting that it may be important in androgen metabolism. Enzymic activity was non-saturable with 3alpha-Diol but saturable with retinoids, although retinoids were not metabolized. Immunohistochemical studies on 10% formalin fixed and paraffin embedded sections of human tissues showed that Pan1b was present in acini and ciliated epithelia of the lung. In the fetus immuno reactivity was present in ciliated epithelia throughout gestation and staining appeared to be stronger in the second half of pregnancy. Pan1b was also expressed in the nonpigmented epithelium of the ciliary body, and in adrenocortical tumor cells. Although 3alpha-Diol is generally considered a degradation product of androgen metabolism it could have its own biological function. Pan1b may be an important modulator of the endocrine, or intracrine activity of this steroid.

17-Hydroxysteroid Dehydrogenases↗
PubMed2001

MRI mapping of cerebrovascular reactivity using square wave changes in end-tidal PCO2.

Cerebrovascular reactivity can be quantified by correlating blood oxygen level dependent (BOLD) signal intensity with changes in end-tidal partial pressure of carbon dioxide (PCO2). Four 3-min cycles of high and low PCO2 were induced in three subjects, each cycle containing a steady PCO2 level lasting at least 60 sec. The BOLD signal closely followed the end-tidal PCO2. The mean MRI signal intensity difference between high and low PCO2 (i.e., cerebrovascular reactivity) was 4.0 +/- 3.4% for gray matter and 0.0 +/- 2.0% for white matter. This is the first demonstration of the application of a controlled reproducible physiologic stimulus, i.e., alternating steady state levels of PCO2, to the quantification of cerebrovascular reactivity.

Adult↗
PubMed2001

Evaluation of HER2 status: for the treatment of metastatic breast cancers by humanized anti-HER2 Monoclonal antibody (trastuzumab) (Pathological committee for optimal use of trastuzumab).

For the treatment of patients with metastatic breast cancer by humanized anti- human epidermal growth factor receptor type 2 (HER2) antibody (trastuzumab), it is important to evaluate HER2 status adequately. "A guideline for HER2 testing" and "HER2 atlas" produced by the "Pathological committee for optimal use of trastuzumab" are introduced in this report. Appropriate evaluations of biological markers are essential for targeting therapy.

Antibodies, Monoclonal↗
PubMed2001

Expression of estrogen receptor alpha and beta in peritoneal and ovarian endometriosis.

OBJECTIVE: To quantify and compare messenger RNA (mRNA) levels of ER-alpha and ER-beta among ovarian endometriotic cysts and red and black peritoneal endometriotic lesions. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Patients with or without endometriosis. INTERVENTION(S): Samples of peritoneal (n = 33) and ovarian endometriotic lesions (n = 37) were obtained during laparoscopic surgery. Normal eutopic endometrial tissues and macroscopically normal peritoneal tissues were obtained as controls during or just after surgery. MAIN OUTCOME MEASURE(S): Expression of mRNA for ER-alpha and ER-beta, using a real-time reverse transcription (RT)-PCR assay, TaqMan RT-PCR, and nonradioactive in situ hybridization (ISH) techniques. RESULT(S): Both eutopic endometrium and endometriotic tissues showed predominantly higher levels of ER-alpha than ER-beta mRNA. Relative ratio of ER-alpha to ER-beta (ER-alpha/ER-beta) mRNA in red peritoneal lesions was significantly higher than in black lesions and ovarian endometriotic cysts. There was no significant difference in ER-alpha/ER-beta between proliferative eutopic endometrium and red peritoneal lesions. These results were confirmed by ISH analysis, which also revealed that the two estrogen receptors were localized in both epithelial and stromal cells of endometriotic tissues. CONCLUSION(S): The predominant expression of ER-alpha in both glandular epithelial and stromal cells may be essential for the development and growth of peritoneal and ovarian endometriosis.

Adult↗
PubMed2001

Aromatase in atherosclerotic lesions of human aorta.

It is well documented that estrogens have atheroprotective effects in humans. Peripheral aromatization of circulating androgens has been demonstrated to exert estrogenic actions in many human tissues, especially in men and post-menopausal women. Recently, production of estrogens mediated by aromatase was detected in cultured smooth muscle cells and aortic endothelial cells and it has been proposed that this in situ produced estrogen may influence the development of atherosclerosis. In this study, we first examined aromatase expression by immunohistochemistry in human aortic tissues obtained from 85 autopsy cases (50 males, 35 females, 49.6 +/- 2.9-year-old) and by mRNA in situ hybridization in 10 cases. We then semi-quantified the level of aromatase mRNA in aortic tissues of 12 men and 12 post-menopausal women by reverse transcriptase-polymerase chain reaction (RT-PCR) to examine whether or not and in which cell types aromatase was expressed. We also studied alternative use of multiple exon 1 of its gene and immunolocalization of 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD I), which converts estrone produced by aromatase to estradiol, a biologically active estrogen. Aromatase immunoreactivity and mRNA hybridization signals and 17beta-HSD I immunoreactivity were all detected in smooth muscle cell (SMC) of the media and thickened intima, especially in SMC adjacent to an atheromatous plaque. The levels of aromatase mRNA were significantly higher in female cases than in male cases (P<0.05). The amount of aromatase mRNA was significantly higher in the specimens with fibroatheroma (P<0.05) than other lesions, and was also significantly higher in the cases utilizing 1c (I.3) or 1d (PII) of exon 1, i.e. gonadal types than those utilizing 1b (I.4), i.e. fibroblasts type as the promoter (P<0.01). These results suggest that estrone and estradiol are produced in SMC of the human aortic wall and that their production is mediated by aromatase and 17beta-HSD I, respectively. Moreover, it was suggested that aromatase overexpression, possibly as a result of alternative splicing, may play some roles in the development of atherosclerosis.

Adolescent↗
PubMed2001

Retinoid receptors in human breast carcinoma: possible modulators of in situ estrogen metabolism.

Retinoid receptors (retinoic acid (RARs) and retinoid X (RXRs) receptors) were immunolocalized in 32 human invasive ductal breast carcinomas. These findings were correlated with clinicopathological parameters to study their biological significance in breast carcinoma. Retinoid receptor immunoreactivity, except for RXRgamma, was detected in the nuclei of carcinoma cells. Percentage of positive cases were RARalpha; 81%, RARbeta; 6%, RARgamma; 28%, RXRalpha; 81%, and RXRbeta; 59%. A significant correlation was detected between RARalpha labeling index (LI), and RXRalpha LI (r = 0.667, p < 0.001). Results from immunoblotting performed in three cases were consistent with those of immunohistochemistry. There was a significant correlation between RARalpha LI and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 1 immunoreactivity (p < 0.05). A significant correlation was also detected between RARalpha (r= 0.413, p = 0.019) or RXRalpha (r = 0.429, p = 0.014) LI, and estrogen receptor (ER) LI. In T-47D breast cancer cells, which express RARalpha, RXRalpha and ER, 17beta-HSD reductive activity increased 1.76-fold (p < 0.001), five days following treatment with 10 nM retinoic acid. These data suggest that retinoid receptors modulate various effects of retinoids, including estrogen metabolism in human breast carcinomas.

Adult↗
PubMed2001

Interleukin-6 (IL-6) producing phaeochromocytoma: direct IL-6 suppression by non-steroidal anti-inflammatory drugs.

A 35-year-old Japanese woman presented with a phaeochromocytoma and demonstrated marked inflammatory reactions and pyrexia as a result of excessive production of interleukin-6 (IL-6) by the tumour. Serum IL-6 level was 262 ng/l (normal; < 4.0 ng/l). Fever and inflammatory markers were largely overcome by the administration of the nonsteroidal anti-inflammatory drug, naproxen, and all symptoms disappeared soon after the tumour was excised. Immunohistochemical study revealed positive staining using an antihuman IL-6 antibody and Northern analysis showed increased IL-6 mRNA levels in the tumour. Cultured tumour cells showed IL-6 protein synthesis, and nonsteroidal anti-inflammatory drugs such as naproxen and indomethacin directly inhibited IL-6 release. These results indicate that the effects of naproxen in vivo were due, at least in part, to direct suppression of IL-6 secretion from the tumour.

Adrenal Gland Neoplasms↗