Production of soluble ICAM-1 from human endothelial cells induced by IL-1 beta and TNF-alpha.

The present study was designed to establish the effects of cytokines on soluble ICAM-1 (sICAM-1) production by human endothelial cells (EC) and ICAM-1 expression on these cells and the effects of purified sICAM-1 on lymphocyte-EC adhesion. Expression of ICAM-1 and production of sICAM-1 were measured by a specific ELISA method. ICAM-1 expression was enhanced by IL-1 beta, TNF-alpha, and most effectively by IFN-gamma. IL-4, IL-6, M-CSF, or GM-CSF showed no effects on ICAM-1 expression. IL-4 (100 units/ml) or IL-6(100 units/ml) abolished the enhancing effect of IL-1 beta, while TNF-alpha (1, 10, 100 units/ml) synergized with IL-1 beta to promote ICAM-1 expression in EC. In contrast with the transient increase of cell-associated ICAM-1 expression after activation by IL-1 beta, which peaked 40 h poststimulation and declined thereafter, sICAM-1 continued to accumulate in culture supernatants even after 48 h poststimulation in IL-1 beta-stimulated EC. IL-1 beta treatment resulted in an increase in adhesion. sICAM-1, purified from cell-free supernatants obtained after a 48-h culture of EC in IL-1 beta by affinity chromatography using monoclonal ICAM-1 antibody coupled to Sepharose beads, significantly inhibited lymphocyte EC adhesion. Preincubation of lymphocytes with conditioned medium of EC cultured with 100 units/ml IL-1 beta for 48 h, which contained a considerable amount of sICAM-1, resulted in a significant inhibition of lymphocyte adhesion to IL-1 beta-stimulated EC. These results suggest that there is a cumulative increase in sICAM-1 concentration in the vicinity of cytokine-stimulated EC and that this sICAM-1 modulates ICAM-1-mediated cell to cell interaction.

Plasma beta-endorphin during fasting in man.

To identify the effects of acute starvation on endogenous opioids in man, plasma beta-endorphin (beta-EP) was measured in 17 patients before, during and after fasting. Patients were assigned a posteriori into two groups: group A, comprised of 11 patients able to tolerate 5-7 days of fasting, and group B, comprised of 6 patients able to tolerate 10 days of fasting. Changes in plasma beta-EP, serum cortisol, circulating nutritional markers, and their relative levels were assessed on the 5th and 10th days of fasting, and on the 5th and 10th days of the refeeding period. Beta-EP had increased by the 5th day (group A: 4.74 +/- 0.42 to 6.91 +/- 0.65 pmol/l, p less than 0.01; group B: 3.60 +/- 0.48 to 5.14 +/- 0.22 pmol/l, p less than 0.05, and remained at 5.05 +/- 0.65 pmol/l on the 10th day (group B: 0.05 less than p less than 0.1) during fasting. Group B had lower levels of plasma beta-EP on the 5th day of fasting than group A (p less than 0.05). However, serum cortisol levels changed similarly in both groups. Plasma beta-EP showed no significant correlation with either the percentage of body weight lost or the body mass index (kg/m2) over this study period. These findings indicate that plasma beta-EP is elevated in the early phase of fasting, while not directly being associated with body weight changes. Plasma beta-EP is lower and less activated in subjects who are able to tolerate fasting for longer periods.

Hormonal and clinical effects of multifollicular puncture and resection on the ovaries of polycystic ovary syndrome.

Sixteen women with polycystic ovary syndrome (PCOS) were treated with laparoscopic multifollicular puncture and resection (MPR), an original technique which we substitute for ovarian wedge resection. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), estrone (E1), estradiol (E2), androstenedione (A) and dehydroepiandrosterone sulphate (DHEAS) were measured daily before and after the operation. Clinically, 15 of the 16 patients (93.8%) exhibited spontaneous ovulation and pregnancies occurred in 8 patients (50%). Significant hormonal changes were observed in serum T. Serum T levels dropped in response to the treatment and remained low for 5 days. Serum E1, A, DHEAS and LH levels were elevated before treatment and did not change after the operation. Serum E2 and FSH levels were within the normal range before the treatment and did not change after the operation. We conclude that surgical treatment for PCOS patients should consist of laparoscopic MPR.

Circadian variations of plasma atrial natriuretic peptide in four types of hypertensive disorder during pregnancy.

Circadian variations in plasma atrial natriuretic peptide were studied, to clarify the characteristic pathophysiology of pregnancy-induced hypertension (PIH). The mean 24-h values (range) of atrial natriuretic peptide in mild and severe PIH, pregnancy-aggravated hypertension, chronic hypertension and normal pregnancy were 130.1 (97.3-207.0), 225.4 (202.8-281.8), 213.1 (183.2-249.5), 81.3 (61.8-116.1) and 77.1 (56.0-123.5) pg/ml, respectively. The values in PIH and pregnancy-aggravated hypertension were significantly higher, although those in chronic hypertension were no different from normal pregnancy. Plasma atrial natriuretic peptide showed a clear circadian rhythm with acrophase in the middle of the night, in mild and severe PIH. In the other hypertensive disorders, a circadian rhythm could not be confirmed. The results indicate that the elevated values of plasma atrial natriuretic peptide in hypertensive disorders during pregnancy relate to generalized vasoconstriction, and that the diurnal rhythm is a specific characteristic of PIH.

Physiologic role of endogenous human atrial natriuretic peptide in preeclamptic pregnancies.

To assess the effect of endogenous human atrial natriuretic peptide on the vascular system in preeclampsia, the circadian variations of plasma human atrial natriuretic peptide, cyclic guanosine 3'5'-monophosphate, cyclic adenosine 3'5'-monophosphate, and blood pressure were measured. In severe preeclamptic women, the mean 24-hour values of human atrial natriuretic peptide and cyclic guanosine 3'5'-monophosphate rose significantly compared with those in normal nonpregnant and pregnant women. Also, in severe preeclamptic women, circadian variations of plasma atrial natriuretic peptide, cyclic guanosine 3'5'-monophosphate, and blood pressure confirmed the same circadian rhythm with acrophase during the middle of the night. Plasma cyclic adenosine 3'5'-monophosphate values did not differ significantly among the three groups and did not confirm a circadian rhythm. These results suggest that plasma human atrial natriuretic peptide may not strongly influence blood pressure, although it may induce the relaxation of vascular smooth muscles via the cyclic guanosine 3'5'-monophosphate system in preeclampsia.

[The clinical and hormonal effects of laparoscopic multiple punch resection (MPR) of the ovary in polycystic ovary syndrome].

Eleven women with polycystic ovary syndrome (PCO) were treated with Laparoscopic Multiple Punch Resection (MPR) of the ovarian follicle and capsule and studied by hormone analysis before and after MPR. In 90.9% of the patients, ovulation appeared to occur within 9 weeks and 63.6% conceived within 26 weeks. No changes in serum LH and FSH levels were seen before and after MPR, but testosterone levels which were in the upper normal range or slightly elevated before treatment were reduced after MPR. Endocrine responses to MPR were similar to those described previously after wedge resection. Laparoscopic MPR is a simple and least invasive method and makes it unnecessary to worry about periovarian adhesion after operation. Furthermore, other causes of infertility can be examined by laparoscopy. MPR appeared to be a promising alternative treatment for patients with PCO.

The effect of laparoscopic multiple punch resection of the ovary on hypothalamo-pituitary axis in polycystic ovary syndrome.

To evaluate the hormonal effect of laparoscopic ovarian punch resection in polycystic ovary syndrome (PCO), seven PCO patients were examined for pulsatile gonadotropin secretions and pituitary sensitivity before and after operation. Marked reductions of luteinizing hormone (LH) pulse amplitudes, mean LH levels, pituitary LH responsiveness, and circulating androgen levels (P less than 0.05) were observed, 3 to 4 days and 6 weeks postoperatively. LH pulse frequency, follicle-stimulating hormone (FSH), and prolactin (PRL) did not change significantly. These results are consistent with the reported hormonal effects of wedge resection and suggest that the impairment of ovarian surface acts on the hypothalamo-pituitary axis to decrease pituitary hypersensitivity and the key factor behind the resultant hormonal change lies not deep inside the ovarian stroma but in the superficial ovarian capsule.

[Laparoscopic diagnosis and evaluation of danazol or gestrinone therapy for endometriosis in sterility].

In forty-six sterile women, endometriosis externa was diagnosed and classified laparoscopically. 21 patients were treated with Gestrinone 5mg-10mg/week and 25 patients were treated with Danazol 300mg-400mg/day for 6 months. The effects of these hormonal treatments were evaluated by second-look laparoscopy according to adhesion severity, number of blueberry spots and chocolate cyst size, as well as dysmenorrhea and other complaints. The results were as follows; 1) Dysmenorrhea was relieved in 60.0% of the Gestrinone-treated group and 45.5% of the Danazol group. 2) Adhesion was weakened or partially separated spontaneously in 66.7% of the Gestrinone group and 63.6% of the Danazol group. 3) Blueberry spots decreased in number or paled in 61.9% of the Gestrinone group and 75.0% of the Danazol group. 4) Chocolate cyst size became smaller in 60.0% of the Gestrinone group and 77.8% of the Danazol group. 5) Peritoneal fluid volume was not decreased after the hormonal treatments but the prostaglandin E2 concentration in peritoneal fluid was decreased (p less than 0.05) after Gestrinone therapy. 6) The patients complained of some side effects, liver function especially was disturbed in 48.0% of the Danazol group and 9.5% of the Gestrinone group. Hoarseness was complained of in 33.3% of the Gestrinone group and 12.0% of the Danazol group. 7) Finally, 23.8% of the Gestrinone group and 28.0% of the Danazol group conceived after the hormonal treatments.

Circadian rhythm of plasma atrial natriuretic peptide, aldosterone, and blood pressure during the third trimester in normal and preeclamptic pregnancies.

The influence of pregnancy on circadian variations of plasma atrial natriuretic peptide and aldosterone was studied. In those women with normal pregnancies, the mean 24-hour values of atrial natriuretic peptide and aldosterone increased, compared with the levels in normal nonpregnant subjects. In cases of severe preeclampsia, levels of atrial natriuretic peptide were significantly higher than in the other subjects, but aldosterone levels decreased to nearly those seen in the nonpregnant subjects. Atrial natriuretic peptide did not establish a rhythm in normal nonpregnant and pregnant subjects, but in the studies of aldosterone levels, a clear circadian rhythm was evident. In severe cases of preeclampsia, atrial natriuretic peptide established a circadian rhythm similar to that of blood pressure, and the circadian rhythm of aldosterone disappeared. The main characteristic of the rhythm in atrial natriuretic peptide and blood pressure in women showing preeclamptic signs is that the acrophase occurred at midnight. This evidence suggests that in women with symptoms of preeclampsia the load to the atria increases at midnight.

Is human atrial natriuretic peptide in fetal blood useful as a parameter to detect the decompensate state of the fetal heart?

In nonimmunologic hydrops fetalis associated with heart anomaly, plasma human atrial natriuretic peptide (hANP) values in umbilical venous blood were significantly higher than those in normal infants. These findings indicate that significant release of hANP from atria is induced by the decompensatory state of the fetal heart.

[The role of "beta-endorphin & beta-lipotropin" on the gonadotropin regulation in the mechanism of human ovulation].

The aim of this study is to elucidate the role of "beta-endorphin (beta-End) & beta-lipotropin (beta-LPH)" on the regulation of gonadotropin (Gn) secretion. We investigated the relationships between immunoreactive beta-End plus beta-LPH and Gn in peripheral plasma of normal menstruating women, 1) during periovulatory period, especially at the time of Gn surge, 2) at the estrogen induced Gn surge (positive feedback) and 3) at the time of hypoxic stress. Plasma concentrations of beta-End plus beta-LPH were measured as immunoreactive beta-End (i-beta-End) by RIA after extraction with Sep-Pak C18. First, we assessed pulsatile Gn secretions during periovulatory period in 19 normal women every 10 minutes for 4 hours, some women were at the time of Gn surge in its ascending limb, plateau of the peak, and descending limb of the surge. Meanwhile, circadian variations of plasma i-beta-End levels of these subjects were assessed at 4 hours' interval on the same day. In two subjects, on the day before the onset of LH surge, significantly low (p less than 0.05) basal and peak levels of i-beta-End were observed, although the basic patterns of circadian rhythm were preserved. Secondly, changes of plasma i-beta-End levels during estrogen (estradiol benzoate 1mg i.m.) induced positive feedback tests were evaluated in 16 normal women and 6 hypothalamic amenorrheic women by daily blood sampling. In normal subjects, small but significant increases (p less than 0.05) of plasma i-beta-End were observed when Gn showed initial decreases at 48 hours after injection. Subsequently at 72 hours, however, plasma i-beta-End decreased precipitously at the time of Gn surge. On the other hand, in hypothalamic amenorrheic women who were devoid of Gn surge, no significant changes of plasma i-beta-End levels were observed. The transient decreases of plasma i-beta-End just prior to the Gn surge support the idea that i-beta-End exerts tonic inhibition on the onset of Gn surge and the disappearance of its inhibition might trigger the positive Gn surge. And it was also suggested that release mechanisms of both i-beta-End and Gn are impaired in hypothalamic amenorrhea. Thirdly, in acute hypoxic stress experiment, 5 normal female volunteers were placed in hypobaric (500 mbar) condition in which oxygen supply is a half of atmosphere, simultaneous blood samplings of Gn, prolactin and i-beta-End were performed every 15 minutes for 3 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

[Laparoscopic diagnosis and evaluation of danazol therapy of endometriosis in sterility].

In twenty two sterile women, endometriosis externa were diagnosed and classified laparoscopically. Classifying the severity of endometriosis by Beecham's and/or Sugimoto's classification, 17 cases were declared mild and only 5 cases severe (one was stage IV and the others were stage III by Beecham's classification, and 4 were grade III by Sugimoto's classification). All these patients were treated with Danazol (Bonzol) 400 mg/day or 300 mg/day for about 24 weeks. Four weeks after the termination of Danazol administration, the effects of Danazol therapy were examined according to the number of blueberry spots, adhesion severity and chocolate cyst size under re-laparoscopy, as well as dysmenorrhea and other complaints. The results were as follows: Dysmenorrhea was relieved in 60.0% of 15 cases, Blueberry spots were decreased or paled in 88.9% of 18 cases, Adhesion was weakened or partially separated spontaneously in 71.4% of 7 cases, Chocolate cyst size became smaller in 85.7% of 7 cases, The patient complained of mild side-effects, namely acne in 45.5% of cases, a weight gain of more than 2 kg in 54.5%, and hoarseness developed in one. The results of laboratory tests performed before and during the treatment remained slightly abnormal or within normal limits.

[Maternal beta-endorphin secretion during pregnancy--measurement of immunoreactive beta-endorphin in urine].

Gestational variations in maternal beta-endorphin (beta-end) secretion were investigated by simultaneous measurements of plasma and urinary immunoreactive beta-endorphin (ir-beta-end). Urinary ir-beta-end was extracted by using a Sep-Pak C18 column and was found to be stable for at least 24 hours at room temperature. Plasma and urine (2 hour collection) samples were obtained from 41 pregnant women and 7 non-pregnant women. Almost parallel increases in plasma and urinary ir-beta-end were observed during the course of pregnancy and there was a good correlation between them. Compared with non-pregnant values, significant increases (p less than 0.001) were observed after 36 weeks of gestation. We also studied chromatographic patterns of urinary extracts of non-pregnant and pregnant women. Both of them consist of 4 peaks and resemble each other. They were essentially similar to those of plasma extracts except for the third peak which appeared between the elution position of beta-lipotropin (beta-LPH) and beta-end. In conclusion, maternal beta-end secretions increase in late gestation not only in plasma but also in urine.

[Modified VAB-3 combination chemotherapy of stage IV endodermal sinus tumor of the ovary].

A case of pure endodermal sinus tumor (EST) of the ovary with huge multiple liver metastases was treated with modified VAB-3 protocol. Serum alpha-fetoprotein (AFP) before treatment was 137,775 ng/ml. A complete clinical response was achieved with rapid shrinkage of liver metastases and normalization of serum AFP. Second-look laparotomy preformed 17 months after the start of chemotherapy revealed no evidence of disease. VAB-3 combination chemotherapy, which was proved to be very effective in the treatment of metastatic testicular cancer, also seems to be effective in the treatment of advanced EST of the ovary. This is believed to be the first detailed report of the successful management of advanced EST of the ovary.