Biomedical subjects

H Sasano

Publications and source records attributed to H Sasano.

At least 109 records · Page 6Linked to original sources

PubMed2000

17beta-hydroxysteroid dehydrogenase type 1 and 2 expression in the human fetus.

The present study investigates the expression patterns of 17beta-hydroxysteroid dehydrogenase (17betaHSD) isozymes in human fetal tissues to understand how estrogenic activity is regulated in the human fetus. Using enzyme assay, high 17betaHSD activity was detected in the placenta and liver, and low levels of 17betaHSD activity were also present in the gastrointestinal tract and kidney. After Northern blot analysis, we detected the messenger ribonucleic acid for 17betaHSD type 1 (17betaHSD1) only in the placenta, whereas that for 17betaHSD type 2 (17betaHSD2) was detected in the placenta, liver, gastrointestinal tract, and urinary tract at 20 gestational weeks. In RT-PCR analysis of the messenger ribonucleic acid transcripts, 17betaHSD 1 was predominantly expressed in the placenta, brain, heart, lung, and adrenal, whereas 17betaHSD2 expression was predominantly detected in the liver, gastrointestinal tract, and kidney. In addition, we detected 17betaHSD2 immunoreactive protein in surface epithelial cells of the stomach, absorptive epithelial cells of the small intestine and colon, hepatocytes of the liver, and interstitial cells surrounding the urinary tubules of the renal medulla. 17betaHSD2 in these tissues may be functioning in the prevention of in utero exposure of the fetus to excessive estradiol from the maternal circulation and amniotic fluids.

17-Hydroxysteroid Dehydrogenases↗

PubMed2000

3beta-hydroxysteroid dehydrogenase/delta5-->4-isomerase activity associated with the human 17beta-hydroxysteroid dehydrogenase type 2 isoform.

The type 2 isoform of human 17beta-hydroxysteroid dehydrogenase (17betaHSD2) efficiently catalyzes the oxidative metabolism of androgens and estrogens, and it is expressed in a large series of human peripheral tissues. To obtain a better understanding of the regulation of local steroid biosynthesis and metabolism in human tissues, we have established a dual steroidogenic activity of the 17betaHSD2 enzyme after transfection of human 17betaHSD2-transfected human embryonic kidney (293) cells. After transient transfection, the metabolism of testosterone, pregnenolone, and dehydroepiandrosterone (DHEA) in intact transfected 293 cells was evaluated by TLC-based radiometric assays. 17betaHSD2-transfected cells converted 91% of testosterone (1 micromol/L) into androstenedione in a 2-h incubation period. In addition, pregnenolone (1 micromol/L) was converted to progesterone (18.5%), whereas DHEA (1 micromol/L) was metabolized to androstenedione (8.3% conversion) in a 15-h incubation period. The kinetics of the 3beta-hydroxysteroid dehydrogenase (3betaHSD) and 17betaHSD2 activities using cell homogenate protein of stably transfected 293 cells indicated that the catalytic efficiency (apparent catalytic efficiency = maximum velocity/Km) of this 3betaHSD activity is approximately 2000-fold (pregnenolone as substrate) or 3000-fold (DHEA as substrate) weaker than that of 17betaHSD2 activity. It is noteworthy, however, that the apparent catalytic efficiency of the HSD3B2 gene product is only approximately 50-fold higher than that of the 3betaHSD aspect of the 17betaHSD2 gene product. Pregnenolone or DHEA effectively inhibited 17betaHSD2 activity in a noncompetitive fashion. Furthermore, the potent 5alpha-reductase/3betaHSD inhibitor, 17beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5alpha-androstane-3-one , inhibited neither 3betaHSD nor 17betaHSD2 activities. We conclude that human 17betaHSD2 enzyme exhibits 3betaHSD activity. Notwithstanding that this 3betaHSD activity is reduced compared to 17betaHSD oxidative activity, it may account for at least some of the reports of 3betaHSD activity found in human peripheral tissues that express notable amounts of the 17betaHSD2 isozyme as well as in individuals with severe classic 3betaHSD deficiency.

17-Hydroxysteroid Dehydrogenases↗

PubMed2000

Ovarian hyperthecosis in the setting of portal hypertension.

Hepatocellular dysfunction and perturbed portal hemodynamics alter steroid metabolism. Men with liver disease have gynecomastia, although women similarly affected rarely show virilization. We report a 10-yr-old girl with portal hypertension and shunting associated with precocious puberty and ovarian hyperandrogenism. This was one of premature twin girls; neither had clitoromegaly or genital ambiguity. In one child, neonatal respiratory problems led to umbilical vein catheterization with subsequent development of portal hypertension. Pubic hair was first noted at age 6 yr, breasts at 7 yr, and severe acne and clitoromegaly at 10 yr. Baseline sex hormones were elevated: androstenedione (A), 413 ng/dL; testosterone (T), 226 ng/dL; and estradiol (E2), 160 pg/mL. Liver transaminases were within the normal range, however, the coagulation profile was mildly abnormal. Cosyntropin adrenal stimulation revealed no steroidogenic defect. Dexamethasone suppression reduced A and T slightly. LH-releasing hormone stimulation produced a pubertal rise in LH and FSH. Pelvic sonography showed a large right ovary with numerous follicles. Surgical exploration revealed symmetrically enlarged ovaries with dense capsules. Histology of ovarian wedge resections showed hyperthecosis; immunohistochemistry showed stromal cells expressing steroidogenic enzymes and proteins. One month postoperatively, A and T were unchanged from baseline, whereas E2 decreased to 56 pg/mL. A single dose of depot leuprolide acetate significantly reduced T. Subsequent treatment with oral contraceptives reduced T to 50 ng/dL, and cyclical menses occurred. We conclude that precocious puberty and ovarian hyperthecosis were induced in this young girl by elevated circulating levels of sex hormones, a consequence of portasystemic shunting and impaired hepatic steroid metabolism.

Androstenedione↗

PubMed2000

11Beta-hydroxysteroid dehydrogenase type II and mineralocorticoid receptor in human placenta.

In mineralocorticoid target organs, 11beta-hydroxysteroid dehydrogenase type II (11beta-HSD2) confers specificity on the mineralocorticoid receptor (MR) by converting biologically active glucocorticoids to inactive metabolites. Placental 11beta-HSD2 is also thought to protect the fetus from high levels of circulating maternal glucocorticoid. In this study, we examined the immunoreactivity of 11beta-HSD2 and MR in human placenta from 5 weeks gestation to full term using immunohistochemistry, 11beta-HSD2 messenger RNA (mRNA) expression using Northern blot analysis, and MR mRNA expression using RT-PCR analysis. Marked 11beta-HSD2 immunoreactivity was detected in placental syncytiotrophoblasts at all gestational stages. MR immunoreactivity was moderately detected in syncytiotrophoblasts, some cytotrophoblasts, and interstitial cells of the villous core. Marked mRNA expression of 11beta-HSD2 was detected in placenta by Northern analysis. RT-PCR analysis of MR in placental tissues showed an amplified product consistent in length with the primers selected. These results suggest that placental 11beta-HSD2 is involved in not only regulating the passage of maternal active glucocorticoids into the fetal circulation but also in regulation of maternal-fetal electrolyte and water transport in the placenta, as in other mineralocorticoid target organs.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed2000

Chicken ovalbumin upstream promoter transcription factor II in the human adrenal cortex and its disorders.

Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an orphan member of the steroid/thyroid hormone receptor superfamily. COUP-TFII has been demonstrated to negatively regulate the transcriptional activity of adrenal 4-binding protein, a steroidogenic cell-specific transcription factor that activates the transcription of various steroidogenic P450 genes. We therefore examined immunolocalization of COUP-TFII in the human adrenal cortex and its disorders, including functioning and nonfunctioning cortical tumors, to study its possible correlation with adrenocortical steroidogenesis. In nonpathological adrenal cortex, COUP-TFII immunoreactivity was marked in the nuclei of adrenocortical cells in definitive and fetal zones from 16 gestational weeks to 2 months after birth. Immunoreactivity for COUP-TFII was marked in the zona glomerulosa and weak in the zonae fasciculata and reticularis from 7 months to 8 yr of age, but thereafter markedly decreased in these zones (P < 0.05, between age 7 months to 8 yr and 24-62 yr of age, respectively). In adrenocortical tumors, COUP-TFII immunoreactivity was marked in the nuclei of tumor cells of aldosteroma (H score, 134 +/- 15.9; P < 0.001 vs. Cushing's adenoma and P < 0.05 vs. nonfunctioning adenoma and carcinoma), modest in nonfunctioning adenoma (82.7 +/- 19.8) and adrenocortical carcinoma (79.6 +/- 56.3), and low in Cushing's adenoma (38.2 +/- 24.5). Results from immunoblotting performed in seven cases of adenomas were consistent with those of immunohistochemistry. In the attached nonneoplastic adrenal cortex of the adenomas, immunoreactivity for COUP-TFII was markedly increased compared to that in nonpathological adrenal cortex in adults and was especially marked in the zona glomerulosa in the attached adrenal of aldosteroma (P < 0.001) and the zona fasciculata in that of Cushing's adenoma (P < 0.05). COUP-TFII immunoreactivity was universally detected in stromal cells of the adrenal glands. These results suggest that COUP-TFII plays an important role in the regulation of steroidogenesis in human adrenal cortex and its disorders.

Adenoma↗

PubMed2000

Developmental roles of the steroidogenic acute regulatory protein (StAR) as revealed by StAR knockout mice.

Steroidogenic acute regulatory protein (StAR) is essential for adrenal and gonadal steroidogenesis, stimulating the translocation of cholesterol to the inner mitochondrial membrane where steroidogenesis commences. StAR mutations in humans cause congenital lipoid adrenal hyperplasia (lipoid CAH), an autosomal recessive condition with severe deficiencies of all classes of steroid hormones. We previously described StAR knockout mice that mimic many features of lipoid CAH patients. By keeping StAR knockout mice alive with corticosteroid replacement, we now examine the temporal effects of StAR deficiency on the structure and function of steroidogenic tissues. The adrenal glands, affected most severely at birth, exhibited progressive increases in lipid deposits with aging. The testes of newborn StAR knockout mice contained scattered lipid deposits in the interstitial region, presumably in remnants of fetal Leydig cells. By 8 weeks of age, the interstitial lipid deposits worsened considerably and were associated with Leydig cell hyperplasia. Despite these changes, germ cells in the seminiferous tubules appeared intact histologically, suggesting that the StAR knockout mice retained some capacity for androgen biosynthesis. Sperm maturation was delayed, and the germ cells exhibited histological features of apoptosis, consistent with suboptimal androgen production. Immediately after birth, the ovaries of StAR knockout mice appeared normal. After the time of normal puberty, however, prominent lipid deposits accumulated in the interstitial region, accompanied by marked luteinization of stromal cells and incomplete follicular maturation that ultimately culminated in premature ovarian failure. These studies provide the first systematic evaluation of the developmental consequences of StAR deficiency in the various steroidogenic organs.

Adrenal Cortex Hormones↗

PubMed2000

A case of renin-producing adrenocortical cancer.

Here we report a case of a renin-producing adrenocortical carcinoma. A 57-year-old woman was referred to our hospital complaining of thirst and generalized muscle weakness. She was diagnosed as being hypertensive and diabetic with associated hypokalemia and she had a hard elastic mass with a diameter of 10 cm on the left side of her neck. An abdominal computed tomography scan revealed a suprarenal mass on the left side (8.5 x 8 x 6.5 cm). Endocrinological examination demonstrated a marked elevation in the patient's serum glucocorticoid and sex steroid hormones as well as plasma renin activity. Histological examination of a sample taken from the neck mass revealed a metastasis from an adrenal carcinoma, which was stained positively with antibodies against cytochrome P450 and renin, establishing the diagnosis of a renin-producing adrenocortical carcinoma. Trilostane was effective in reducing serum cortisol levels, but mitotane was ineffective.

17-Hydroxycorticosteroids↗

PubMed2000

17Beta-hydroxysteroid dehydrogenase type 2 and dehydroepiandrosterone sulfotransferase in the human liver.

The liver plays important roles in the clearance and metabolism of sex steroids. Its dysfunction is considered to influence the metabolic pathways of sex steroids, and to result in gynecomastia and other abnormalities of sex steroids. However, the details of its mechanism have not been well-characterized. We therefore examined the enzymes involved in the hepatic clearance and/or metabolism of sex steroids in human liver and its disorders using immunohistochemistry to determine whether there are any abnormalities of expression of these enzymes in human liver disorders. These enzymes are 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 2, an enzyme that catalyzes the biologically active estrogen, estradiol (E2), to inactive estrogen, estrone (El), and dehydroepiandrosterone sulfotransferase (DHEA-ST), which catalyzes sulfonation of dehydroepiandrosterone (DHEA) to form biologically inactive DHEA-S. A total of 162 cases including normal liver (n=31), chronic hepatitis (n=41), liver cirrhosis (n = 21), hepatocellular carcinoma (n = 47), cholangiocellular carcinoma (n = 22) and fetal liver (n = 4) were examined by immunohistochemistry. Both enzymes were expressed in the hepatocytes around portal area and central vein in normal liver. Immunopositive area for DHEA-ST was significantly larger in chronic hepatitis than in normal liver, but that of 17beta-HSD type 2 in chronic hepatitis was not different from normal liver. There were no significant differences in the immunopositive area for both enzymes between liver cirrhosis and normal liver. In hepatocellular carcinoma, immunoreactivity for both enzymes were categorized into Group A, or low positive group, and Group B, or high positive group. The latter tended to be poorly differentiated carcinoma. In cholangiocellular carcinoma, immunopositive areas of both enzymes were significantly smaller than those of normal liver. These findings indicate that the amount of expression of the enzymes involved in metabolism and/or clearance of sex steroids per hepatocyte did not decrease in liver cirrhosis. Therefore, sex steroids' abnormalities may be due to the decreased quantity of hepatocytes associated with liver cirrhosis. In hepatocellular carcinoma, some poorly differentiated cases were associated with increased expression of 17beta-HSD type 2 but its biological significance needs to be determined by further studies.

17-Hydroxysteroid Dehydrogenases↗

PubMed2000

Estrogen biosynthesis in endometriosis: molecular basis and clinical relevance.

Conversion of C(19) steroids to estrogens is catalyzed by aromatase in human ovary, placenta and extraglandular tissues such as adipose tissue, skin and the brain. Aromatase activity is not detectable in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis and is stimulated by prostaglandin E(2) (PGE(2)).( )This results in local production of estrogen, which induces PGE(2) formation and establishes a positive feedback cycle. Another abnormality in endometriosis, i.e. deficient hydroxysteroid dehydrogenase (17beta-HSD) type 2 expression, impairs the inactivation of estradiol to estrone. These molecular aberrations collectively favor accumulation of increasing quantities of estradiol and PGE(2 )in endometriosis. The clinical relevance of these findings was exemplified by the successful treatment of an unusually aggressive case of postmenopausal endometriosis using an aromatase inhibitor.

Anastrozole↗

PubMed2000

[Tracheal tube/laryngeal mask exchange to prevent coughing in lung volume reduction surgery].

We report the use of laryngeal mask airway (LMA) to facilitate smooth emergence from anesthesia in 3 patients who underwent lung volume reduction surgery (LVRS) for severely symptomatic emphysema. To prevent coughing during emergence we replaced the endotracheal tube with LMA while patient was still in deep anesthesia. Emergence was smooth without coughing in all three patients, and ventilation with facemask was not needed after removal of LMA. We believe this technique is safe and beneficial for anesthetic management of LVRS.

Aged↗

PubMed1999

Expression of 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD-2) in the developing human adrenal gland and human adrenal cortical carcinoma and adenoma.

The aim of this study was to investigate the ontogeny of localization of 11betaHSD-2 protein in the human adrenal gland. In addition, we have investigated the effects of abnormal adrenal function on 11betaHSD-2 by determining the pattern of localization of 11betaHSD-2 protein, and the amount and level of expression of 11betaHSD-2 mRNA and protein in human adrenal cortical carcinoma and adenoma. In the human foetal adrenal gland 11betaHSD-2 immunoreactivity (11betaHSD-2-ir) was detected in the foetal zone, whereas in normal adult adrenal glands 11betaHSD-2-ir was not detected by immunocytochemistry. In adrenal cortical carcinoma and adenoma, 11betaHSD-2-ir was detectable in specific regions, which have been identified as steroid synthesizing cells using 3betaHSD-ir as a marker. In adrenal cortical carcinoma and adenoma, 11betaHSD-2 mRNA and 11betaHSD-2 protein were detected by nuclease protection analysis and by western blot analysis, respectively. In summary, 11betaHSD-2-ir was detected in the foetal zone of the mid-gestation human foetal adrenal, whereas, 11betaHSD-2-ir was not detectable in the postnatal or normal adult adrenal gland. 11BetaHSD-2 protein and mRNA was induced in adult human adrenal cortical carcinoma and adenoma. The induction of expression of 11betaHSD-2 in the adrenal cortex suggests a possible role in regulating abnormal adrenal steroidogenic function in these patients.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1999

Effects of sympathetic nerve blockades on low-frequency oscillations of human earlobe skin blood flow.

Earlobe skin blood flow measured by laser Doppler flowmetry often shows low-frequency oscillations with a frequency around 0.1 Hz. We evaluated the effects of different sympathetic blocking techniques on the oscillations. Power spectrum of 5-min time series of beat-to-beat peak earlobe skin blood flow showed a distinct spectral peak at a frequency around 0.1 Hz (mean +/- SD, 0.107+/-0.016 Hz). The power of the spectral peak measured as coefficient of component variance (CCV) was diminished with total spinal anesthesia (TSA, n = 4) and cervicothoracic epidural anesthesia (CTEA, n = 4; P<0.05 for both). The CCV was unchanged significantly with bilateral thoracic sympathetic ganglionic excision (TSGE, n = 5). Right stellate ganglion block (RSGB, n = 6) caused a trend towards an increase in the CCV on the right (blocked)-side (P = 0.072) but no change on the left (intact)-side. Cross-spectrum analysis revealed that the low-frequency oscillations were not coherent between the right- and left-side earlobes or with low-frequency oscillations in systolic blood pressure either before or after RSGB. TSA and CTEA are known to cause extensive sympathetic nerve blockade in a broad area, while TSGE and RSGB are known to cause local and partial sympathetic blockade. Our results suggest that although the low-frequency oscillations in earlobe skin blood flow may be mediated non-neurally, magnitude of the oscillations may be modified by sympathetic vasomotor tone.

Adult↗

PubMed1999

Localized expression of aromatase in human vascular tissues.

The atheroprotective effects of estrogen are well established and the presence of an estrogen receptor in vascular tissues has recently been reported. Therefore, we investigated the localization of the estrogen-producing enzyme aromatase in vascular tissues to assess the possible contribution of endocrine, paracrine, and autocrine modes of action. Aromatase was found in human vascular smooth muscle cells (SMCs) but not in endothelial cells on in situ hybridization. These observations were further supported by quantitative analysis of aromatase mRNA and the activity in 15 human vascular specimens. Only trace levels of expression were detected in the 3 infants examined, whereas 0.0088 to 0.0806 amol/ microg RNA of aromatase mRNA and 12.9 to 122.3 fmol. h-1. mg-1 protein of the activity were detected in 12 of the adult individuals. The switching of tissue-specific exon 1 of the human aromatase gene was also observed in some cases. Aromatase was found to be expressed only in cultured SMCs and not in cultured endothelial cells of human aorta and pulmonary artery and to be regulated through dexamethasone and the signaling pathways of protein kinase A and C. Study results revealed the localized expression of aromatase in vascular SMCs, which indicated a possible direct action of locally produced estrogen in an autocrine or paracrine manner, with possible cross talk between smooth muscle and endothelial cells.

Adolescent↗

PubMed1999

Structural and functional abnormalities in the spleen of an mFtz-F1 gene-disrupted mouse.

The spleen has two main functions. The first is to provide a proper microenvironment to lymphoid and myeloid cells, whereas the second involves clearance of abnormal erythrocytes. Ad4BP/SF-1, a product of the mammalian FTZ-F1 gene (mFTZ-F1), was originally identified as a steroidogenic, tissue-specific transcription factor. Immunohistochemical examination of the mammalian spleens confirmed the expression of Ad4BP/SF-1 in endothelial cells of the splenic venous sinuses and pulp vein. In mFtz-F1 gene-disrupted (KO) mice, several structural abnormalities were detected in the spleen, including underdevelopment and nonuniform distribution of erythrocytes. Examination of the spleen of KO fetuses showed failure of development of certain tubular structures during embryogenesis. These structures are normally assembled by Ad4BP/SF-1 immunoreactive cells, and most likely form the vascular system during later stages of development. Other structural abnormalities in the spleen of the KO mice included defects in the tissue distribution of type-IV collagen, laminin, c-kit, and vimentin. These morphologic defects in the vascular system were associated with a decrease in the proportion of hematopoietic cells, although differentiation of these cells was not affected significantly. A high number of abnormal red blood cells containing Howell-Jolly bodies were noted in the KO mice, indicating impaired clearance by the splenic vascular system. We also detected the presence of an mRNA-encoding cholesterol side-chain cleavage P450 in the spleen, resembling the findings in steroidogenic tissues such as the gonads and adrenal cortex. The mRNA transcript was not involved in splenic structural defects as it was detected in the spleens of both normal and KO mice, indicating that the regulatory mechanism of the P450 gene in the spleen is different from that in steroidogenic tissues. Our results indicate that a lack of the mFtz-F1 gene in mice is associated with structural and functional abnormalities of the splenic vascular system.

Animals↗

PubMed1999

Superoxide dismutase in normal cycling human ovaries: immunohistochemical localization and characterization.

OBJECTIVE: To investigate the expression of manganese (Mn) and copper-zinc (Cu,Zn) superoxide dismutase (SOD) in normal cycling human ovaries throughout the menstrual cycle. DESIGN: Descriptive, controlled study. SETTING: Tohoku University School of Medicine. PATIENT(S): Twenty-four normal cycling human ovaries were obtained from patients who underwent oophorectomy and hysterectomy for squamous cell carcinoma of the uterine cervix. INTERVENTION(S): Immunohistochemistry for Mn-SOD and Cu,Zn-SOD. MAIN OUTCOME MEASURE(S): Immunostaining. RESULT(S): In the follicular stage, Mn-SOD immunoreactivity was detected in granulosa and theca interna cells of steroid-producing follicles, that is, preantral, nondominant, dominant, and atretic follicles, whereas Cu,Zn-SOD was detected in theca interna cells of these follicles and in granulosa cells of dominant follicles. In the luteal stage, immunoreactivity for Mn-SOD and Cu,Zn-SOD was observed in both luteinized granulosa and theca cells of the functioning corpus luteum. In the early degenerating corpus luteum, both Mn-SOD and Cu,Zn-SOD were positive in steroid-producing luteinized theca cells. Mn-SOD immunoreactivity was also detected in nonsteroid-producing luteinized granulosa cells and macrophages. CONCLUSION(S): Our results suggest that the expression of Mn-SOD and Cu,Zn-SOD closely correlates with steroidogenesis in the human ovary. In addition, Mn-SOD may play an important role in the process of luteal regression.

Adult↗

PubMed1999

Lipoprotein lipase promoting agent, NO-1886, modulates adrenal functions: species difference in effects of NO-1886 on steroidogenesis.

A novel compound, NO-1886, which possesses a powerful lipoprotein lipase activity-increasing action, induces hypertrophy of adrenals in rats and hyperplasia of cortical cells in dogs. However, these effects were not observed in monkeys. We examined the effects of NO- 1886 on steroid hormone production by adrenocortical cells to clarify its effects on adrenal steroidogenesis. NO-1886 did not inhibit the steroid synthetic enzymes, including 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase, 11beta-hydroxylase, or cholesterol side-chain cleavage enzymes. However, NO-1886 affected steroid production from adrenocortical cells in rats, dogs, monkeys, and humans in in vitro studies. These effects were almost completely reversed by the addition of 25-hydroxycholesterol or low-density lipoproteins to the reaction medium, but not reversed by the addition of high-density lipoproteins. These results suggest that NO-1886 affects the cholesterol pathways within the adrenocortical cells and inhibits steroidogenesis, causing a reduction of steroid hormone release from adrenocortical cells and resulting in hypertrophy of adrenals via feed-back mechanisms. However, its effect is not apparent in animals that use low-density lipoproteins as a source of adrenocortical steroidogenesis.

Adrenal Cortex↗

PubMed1999

Cell damage and proliferation in human gastric mucosa infected by Helicobacter pylori--a comparison before and after H pylori eradication in non-atrophic gastritis.

Helicobacter pylori (HP) is believed to be involved in the transition from normal gastric mucosa to atrophic gastritis and intestinal metaplasia. Infection with the organism is one of the risk factors for development of intestinal-type gastric adenocarcinoma, possibly through altered cell turnover. Medical eradication of HP is widely performed for the treatment of peptic ulcers and other upper gastrointestinal disorders. Eradication of HP may affect altered cell turnover of the gastric mucosa caused by the infection, but there are few reports comparing sterilized mucosa with HP-infected and non-infected mucosa. In this study, we examined cell damage using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL), in situ nick translation (ISNT), and cell proliferation by Ki 67 immunohistochemistry staining in gastric mucosa before and after HP eradication and in non-infected gastric mucosa. We then compared these findings using endoscopic gastric biopsy specimens. Labeling indices of TUNEL (2.46 +/- 1.22), ISNT (1.13 +/- 0.42), and Ki67 (21.8 +/- 6.14) in tissue from which HP had been eradicated were significantly lower than those of HP-infected mucosa (6.36 +/- 2.26, 4.00 +/- 1.62, 45.8 +/- 5.35, for TUNEL, ISNT, and Ki67, respectively). There were no significant differences between formerly infected and non-infected mucosa (TUNEL: 2.26 +/- 0.69, ISNT: 1.29 +/- 0.63, Ki67: 23.5 +/- 8.20). These results indicate that medical HP eradication results in decreased cell proliferation and damage, restoring the condition seen in non-infected mucosa. Thus, HP eradication may be effective, not only in the treatment of gastric ulcers or gastric symptoms, but also in the prevention of gastric carcinoma.

Anti-Bacterial Agents↗

PubMed1999

Urocortin in human placenta and maternal plasma.

Plasma immunoreactive (IR-) urocortin (Ucn) and corticotropin-releasing factor (CRF) levels in pregnant women were measured by their specific radioimmunoassays after extraction. Although plasma IR-CRF levels were increased in pregnant women as compared to men and non-pregnant women, there was no difference of plasma IR-Ucn levels among groups. Ucn mRNA was detected in cytotrophoblasts and syncytiotrophoblasts by in situ hybridization. A reverse-phase high-performance liquid chromatography (HPLC) showed the major peak of IR-Ucn in placenta and plasma that had similar chromatographic mobility to synthetic Ucn1-40. These data suggest that Ucn is produced and processed into the same form of synthetic Ucn in placenta, but not secreted into maternal blood.

Adult↗