Increased expression of perforin, granzyme B, and C5b-9 in villitis of unknown etiology.

INTRODUCTION: Villitis of unknown etiology (VUE) is associated with fetal growth restriction. However, the underlying mechanisms of villous injury in placentas with VUE are still largely unknown. We aimed to verify whether apoptosis-related factors are increased in VUE placentas. Furthermore, we determined apoptosis of villous cells. METHODS: Six placentas with VUE and 3 control placentas were stained using immunohistochemistry with antibodies for CD3, CD4, CD8, CD68, CD163, perforin, granzyme B, granzyme K, and C5b-9. TUNEL assay analysis was also performed with these placentas. The percentage of cells that stained positive, CD163/CD68 ratio, percentage of C5b-9 positive area, and apoptosis index were quantified and compared between the inflammatory lesions of the VUE placentas, non-VUE inflammatory lesions of the VUE placentas, and control placentas. RESULTS: The percentages of CD3, CD4, CD8 CD68, CD163, perforin, and granzyme B positive cells were significantly higher in the inflammatory lesions of the VUE placentas (p < 0.05). The intravillous CD163/CD68 ratio was higher in the inflammatory lesions compared with the non-inflammatory lesion of the VUE placentas (p < 0.05). The percentage of granzyme K-positive cells was not significantly different between the groups. C5b-9 deposition was higher in the inflammatory lesions of the VUE placentas (p < 0.05). TUNEL-positive cells were significantly higher in the inflammatory lesions of the VUE placentas (p < 0.05). DISCUSSION: To the best of our knowledge, this is the first report to assess villous injury, especially from a viewpoint of villous apoptosis in VUE placentas. An activated perforin/granzyme pathway and C5b-9 are suggested as possible mechanisms of apoptosis.

Bone mineral density of the spine and proximal femur in normal and osteoporotic subjects in Japan.

Bone mineral density (BMD) of the spine and proximal femur in Japanese men and women was investigated with dual photon absorptiometry, using gadolinium-153. Peak bone mass of the spine (L2-4) was 1.20 g/cm2 in women which was lower than that of men by 4.7%, whereas BMD of the femoral neck was 0.91 g/cm2 in women and lower than in men by 13.3%. Bone loss was faster in postmenopausal women than in men of the corresponding age, and the regressions of BMD on age were 6.7-times higher at L2-4 and 5.1-times higher at the femoral neck than in men. Such rates of loss became slower both in the lumbar spine and proximal femur in women after 70 years of age, but the density at the proximal femur kept decreasing in men after 70 years of age. Fracture thresholds of each region were evaluated at the 90th percentile for BMD of L2-4 in patients with vertebral crush fractures and for BMD of the proximal femur in patients with hip fractures. The fracture threshold was 0.97 g/cm2 at the spine and 0.67 g/cm2 at the femoral neck in women. BMD values at the spine and proximal femur in normal Japanese men and women appear to be lower than those in white American control population.

Serum relaxin and steroid hormones in spontaneous abortions.

To assess the capacity of the corpus luteum to secrete steroid hormones and relaxin during spontaneous abortion, human chorionic gonadotropin (hCG), progesterone, 17 alpha-hydroxyprogesterone (17-OHP) and relaxin concentrations were determined in serum samples obtained from 16 spontaneously aborting first-trimester patients and 5 asymptomatic, apparently normal women who subsequently aborted. hCG and P were subnormal in more than half of aborting patients, and 17-OHP in half of them. However, relaxin was normal in most of them. No patient with subnormal relaxin levels had hCG values in the normal range. Such a relationship was not found between hCG and 17-OHP values. Hence, decreases in placental activity seem to precede a decrease in luteal ability to secrete relaxin but not to secrete steroid hormones. Some aborting patients with subnormal 17-OHP levels had normal relaxin values. All but 1 woman who aborted subsequently had subnormal 17-OHP values at a time when relaxin levels were normal. Therefore, in some aborting patients, the ability of the corpus luteum to secrete steroid hormones is impaired at a time when its capacity to secrete relaxin is preserved.

Tibial artery autogenous in situ vein bypass with adjunctive arteriovenous fistula.

A man suffering from severe intermittent claudication of the right calf and foot was successfully treated by femoro-tibio-peroneal trunk autogenous vein bypass with adjunctive arteriovenous fistula. Prior to operation, he was unable to walk more than 50 meters without resting. Preoperative arteriography revealed extensive occlusion of the popliteotibial arteries, except for indistinct visualization of the tibio-peroneal trunk, in which conventional reconstructive surgery seemed not to be feasible because of poor distal run-off. An autogenous vein bypass graft between the distal superficial femoral artery and tibio-peroneal trunk was successfully made "in-situ", creating an adjunctive arteriovenous fistula. Postoperatively, the ankle pressure index of the posterior tibial artery was considerably increased from 0 to 0.65, and Doppler flow wave could be recorded. The patient can now walk more than 1,500 meters without resting.

Changes in plasma oxytocin, prostaglandin E1, and 13,14-dihydro-15-keto-prostaglandin F2 alpha during labor induced by prostaglandin E2 or F2 alpha and spontaneous labor.

To observe the changes in endogenous oxytocics during spontaneous and induced labor, the plasma concentrations of oxytocin, prostaglandin E1 (PGE1) and 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) were measured during labor in 9 cases of spontaneous labor (group 1), 10 of PGE2-induced labor (group 2), and 7 of PGF2 alpha-induced labor (group 3). Unextracted samples were used for radioimmunoassay of oxytocin. PGE and PGF were extracted and separated for radioimmunoassays of PGE1 and PGFM. Although oxytocin levels in groups 1 and 3 did not change during labor or slightly increased toward delivery, those in group 2 decreased as labor progressed. The mean oxytocin in group 2 was significantly lower at the times of established labor (15.3 +/- 3.2 microU/ml, mean +/- SE) and crowing of the fetal head (10.8 +/- 2.0 microU/ml) than before labor (52.7 +/- 14.8 microU/ml). Plasma PGE1 levels in groups 1 and 3 were low and did not change during labor. Plasma PGFM levels in groups 1 and 2 gradually rose toward delivery. These results suggest that exogenous PGE2 suppresses oxytocin secretion during labor and stimulates endogenous PGF2 alpha production, that endogenous PGE1 may not play an important role in the progress of spontaneous and PGF2 alpha-induced labor, and that endogenous PGF2 alpha may participate in the promotion of all kinds of labor.

Antithrombotic and vasodilating effects of OP-41483, a prostacyclin derivative.

Anti-platelet and vasodilating actions of OP-41483, a derivative of prostacyclin, were studied experimentally and clinically. The ADP-induced human platelet aggregation was significantly inhibited in vitro, the rate being 59% with a dose of 3 micrograms/ml, 75% with 6 micrograms/ml and over 90% with 18 micrograms/ml or more. A significant reduction in deposition of platelet and mural thrombi on the chemically injured luminal surface of the canine femoral vein was observed by treatment with topical administration of the solution (10 micrograms/ml) and/or intravenous infusion (10 ng/kg/min). The blood flow rate of the normal canine femoral artery and the anterior or posterior tibial artery of patients with peripheral arterial occlusive disease at the ankle was moderately increased in cases of intravenous infusion of the compound at a rate of 10 ng/kg/min.

Serum relaxin concentrations in women following the administration of 16,16-dimethyl-trans-delta 2-PGE1 methyl ester during early pregnancy.

Serum relaxin was estimated in 11 women during termination of first-trimester pregnancy with 16,16-dimethyl-trans-delta 2-PGE1 methyl ester (16 DM-PGE1). Vaginal administration of 16 DM-PGE1 was associated with a significant increase in serum relaxin.

PIP: The effect of prostaglandin on relaxin secretion in early pregnancy has not been established. To gain more information on this process, the association between administration of a derivative of prostaglandin El (PGE1)--16,16-dimethyl-trans-delta2-PGE1 methyl ester (16 DM-PGE1)--on serum relaxin levels was investigated in 11 women presenting for 1st- trimester abortion. A vaginal suppository of 1 mg of 16 DM-PGE1 was inserted in the posterior vaginal fornix of study subjects every 3 hours for a maximum of 5 applications. Both relaxin and progesterone levels were measured by radioimmunoassay. 8 of the 11 subjects aborted. Mean basal concentrations of relaxin and progesterone were 1.1 + or - 0.2 and 21.9 + - 8.0 ng/ml, respectively. Serum relaxin levels were significantly increased over baseline levels 1, 2, 3, and 6 hours after 16 DM-PGE1 administration, even in subjects whose pregnancies were not terminated, but there was no effect on serum progesterone levels. Since relaxin is considered to provide an accurate indicator of luteal function, these results suggest that 16 DM-PGE1 is luteolytic in humans.

Serum relaxin in patients with invasive mole, choriocarcinoma and persistent trophoblastic disease.

Human chorionic gonadotropin (hCG) is considered to be one of the factors which regulate relaxin secretion in humans. Serum immunoreactive relaxin levels are increased and are detectable by radioimmunoassay both in normal and molar pregnancy. Circulating hCG levels are increased in trophoblastic disease. In the present study, relaxin and hCG levels were sequentially measured in patients with invasive mole, choriocarcinoma and persistent trophoblastic disease. Serum relaxin levels were detectable by radioimmunoassay in these patients before treatment, though they were significantly lower than in normal pregnancy. The corpus luteum of pregnancy is the main source of circulating relaxin in normal pregnancy. The existence of a corpus luteum was confirmed in the 2 patients who underwent laparotomy. Consequently, the corpus luteum may also be the main source of circulating relaxin in trophoblastic disease. Parallel changes in hCG and relaxin levels were observed during the courses of trophoblastic disease. The finding suggests that relaxin secretion is dependent on hCG stimulation in trophoblastic disease in the presence of corpus luteum.

Serum relaxin in patients with hydatidiform mole.

Human chorionic gonadotropin (hCG) is considered to be one of the factors that regulates relaxin secretion in humans. However, the secretory pattern of relaxin has not been evaluated in pregnancy complicated by hydatidiform mole, where circulating hCG levels are higher than in normal pregnancy. In the present study, relaxin, progesterone, and hCG levels were determined by radioimmunoassay in patients with hydatidiform mole before and after evacuation of the mole. Serum immunoreactive relaxin and progesterone levels in patients with hydatidiform mole were similar to those in normal women at corresponding weeks of pregnancy before evacuation of the mole, though hCG levels were significantly higher. The fall of relaxin levels after evacuation of the mole was slower than that of hCG or progesterone. This finding may reflect a continued stimulation of the corpus luteum by lower, but still effective, hCG levels persisting after evacuation of the mole. An extraluteal source of relaxin cannot be excluded.

Increased serum CA 125 levels during the first trimester of pregnancy.

An immunoradiometric assay for an ovarian tumor associated antigen (CA 125) has recently been developed. The CA 125 assay was reported to be fairly sensitive for ovarian cancer. However, elevated CA 125 levels were reportedly observed in 1% of healthy controls, 6% of patients with miscellaneous diseases and 29% of patients with non-gynecological cancer. Therefore, the specificity of the CA 125 assay must be evaluated before its wide clinical application. Furthermore, data on the CA 125 levels in pregnant women have not heretofore been reported. In the present study, CA 125 levels were determined in sera randomly obtained from normal, pregnant women at various weeks of pregnancy and in sera serially collected from women who achieved pregnancy after ovulation induction. When compared with the normal, non-pregnant state, CA 125 levels in pregnant women were significantly higher during the first trimester, but not during the second and third trimesters. Although CA 125 levels in women during the first trimester of pregnancy were significantly lower than those in patients with ovarian cancer, there was a considerable overlap between them. CA 125 levels were undetectable before pregnancy in all of the 8 patients who achieved pregnancy after ovulation induction. They rose during the first trimester of pregnancy in 7 of the 8 patients, and they decreased thereafter to undetectable levels by the end of the first trimester. The increased CA 125 level in the early pregnancy provides an important information for the clinical application of the CA 125 assay. Pregnancy should be ruled out when increased CA 125 levels are found in women during the childbearing years.

The secretory patterns of relaxin and human chorionic gonadotropin in human pregnancy.

Relaxin and human chorionic gonadotropin (hCG) were simultaneously determined in the same serum samples obtained from pregnant women. Although the secretory pattern of relaxin, in general, appeared to parallel that of hCG during human pregnancy, several discrepancies were discerned in the secretory patterns of the two hormones. The mean hCG concentration significantly differed between weeks 4-7 and 8-11 of pregnancy, but the mean relaxin concentration did not. The mean relaxin concentration began to decrease at weeks 16-19 whereas that of hCG did so at weeks 12-15. The mean relaxin concentration at weeks 4-7 was significantly higher than that at weeks 24-27, though there was no significant difference between the mean hCG concentrations in the two periods. These differences in the secretory pattern of relaxin from that of hCG indicate that relaxin secretion in pregnancy is not determined only by the circulating level of hCG. The responsiveness of the corpus luteum of pregnancy to hCG stimulation of relaxin secretion may vary as a function of the age of the corpus luteum, and this may partially account for the differences between the secretory pattern of relaxin and that of hCG observed in the present study.

Twenty-four hour secretory pattern of thyroid-stimulating hormone in hyperprolactinemic women with pituitary microadenoma.

In order to determine whether endogenous dopaminergic tone has any role in the diurnal variation in TSH secretion, the 24-h secretory pattern of TSH and the TSH response to a dopamine antagonist, metoclopramide (MCP), were evaluated in normal women (n = 4) and in hyperprolactinemic-amenorrheic women with pituitary microadenoma (n = 6). TSH concentrations expressed as percent deviation from the 24-h mean significantly differed with respect to time of day in normal women and hyperprolactinemic women. They were significantly higher during the night (2000-0700 h) than during the daytime (0800-1900 h). Whereas MCP administration induced no significant changes in serum TSH levels in normal women, it significantly increased serum TSH levels in hyperprolactinemic women. Thus, the diurnal variation in TSH secretion was demonstrated in hyperprolactinemic women with pituitary microadenoma in the face of an increased dopaminergic inhibition of TSH secretion. The present study did not provide evidence that the diurnal pattern of TSH secretion is related to the endogenous dopaminergic tone.

Five-year clinical evaluation of the St. Jude Medical valve prosthesis in 136 patients.

One hundred and thirty-six patients (June 1979, through May 1984) underwent mitral, aortic or double valve replacement and apico-aortic bypass with the St. Jude Medical (SJM) prosthesis, at Ryukyu University Hospital, Okinawa. Operative mortality for the entire group was 4.4 per cent. Late mortality from 1979-1984 was 6.1 per cent. There were no deaths related to mechanical failure. Warfarin anticoagulation was recommended for all patients. The incidence of thromboembolism was 0.76/100 patient years. Post operative catheterization studies in 21 patients one year after operation showed a satisfactory recovery of cardiac function. The SJM valve seems to be the satisfactory artificial valve in present use.

Functional evaluation of the adenohypophysis with metoclopramide in hyperprolactinemic-amenorrheic women in relation to radiological findings on the sella turcica.

The responses of the adenohypophyseal hormones to metoclopramide (MCP) were evaluated in hyperprolactinemic women with various radiological findings on the sella turcica. Serum PRL concentrations significantly increased after MCP administration in normal women, hyperprolactinemic patients with normal sella and patients with microadenoma, but not in macroadenoma patients with and without suprasellar expansion (SSE). The PRL response to MCP administration was significantly lower in hyperprolactinemic patients than in normal women. Serum TSH concentrations significantly increased after MCP administration in each group of subjects. The TSH response to MCP was significantly higher in patients with normal sella and patients with microadenoma than in normal women. However, the responses of PRL and TSH to MCP were not significantly different between patients with normal sella and patients with microadenoma. Therefore, they were not considered useful in distinguishing tumorous from nontumorous hyperprolactinemia. Serum LH concentrations significantly increased after MCP administration in patients with normal sella, patients with microadenoma and macroadenoma patients without SSE, but not in normal women or macroadenoma patients with SSE. The LH response to MCP was significantly higher in patients with microadenoma than in patients with normal sella. Serum FSH concentrations significantly increased after MCP administration only in patients with microadenoma. The different responses of the adenohypophyseal hormones to MCP in hyperprolactinemic women with various radiological findings on the sella turcica may be explained by the difference in the hypothalamic dopamine activity and in the impairment of the hypothalamic-pituitary system due to pituitary tumor.

Twenty-four hour secretory pattern of prolactin in hyperprolactinaemic patients with pituitary micro- and macroadenomas.

No nocturnal increase of prolactin (Prl) secretion during sleep has reportedly been discernible in most cases of hyperprolactinaemic patients with pituitary tumour. However, subjects previously evaluated, were in the majority, patients with large pituitary tumour. In the present study, 24 h secretory pattern of Prl was evaluated in 4 hyperprolactinaemic women with pituitary microadenoma and in 4 hyperprolactinaemic women with pituitary macroadenoma. Nocturnal increase of Prl secretion was observed in patients with microadenoma, but not in patients with macroadenoma. The nocturnal increase of Prl secretion in patients with microadenoma may reflect the function of the adenoma cells, and may suggest that the basic central nervous system programme governing Prl secretion in normals is qualitatively preserved in these patients. Alternatively, the nocturnal increase of Prl secretion may reflect the function of the normal lactotrophs remaining in these patients.

Comparison of plasma oxytocin levels during spontaneous labor and labor induced by amniotomy, prostaglandin F2 alpha, and prostaglandin E2.

Plasma concentrations of oxytocin in nine spontaneous labors (group 1), nine amniotomy-induced labors (group 2), six prostaglandin F2 alpha-induced labors (group 3), and five prostaglandin E2-induced labors (group 4) were determined at the stages of 1 to 7 days preceding the onset of labor, onset of labor, and established labor, by means of unextracted radioimmunoassay. The levels of oxytocin in the stage preceding the onset of labor in group 1 were not significantly different from the levels of oxytocin in the corresponding stages in groups 2, 3, and 4. However, the levels of oxytocin in the stages of onset of labor and established labor in group 1 were significantly higher than those in the corresponding stages in groups 2, 3, and 4. These results suggest that oxytocin plays a leading role in the onset and progress of spontaneous labor, whereas something other than oxytocin might be involved in the labor induced by amniotomy alone or by prostaglandins.

Acute febrile mucocutaneous lymph node syndrome with multiple aneurysms: report of a case.

A 4-month-old male infant with acute febrile mucocutaneous lymph-node syndrome developed mitral regurgitation, pericardial effusion and multiple pulsating masses in the upper and lower extremities. Two-dimensional echocardiography demonstrated aneurysms in both coronary arteries. Arteriography of the right arm demonstrated multiple aneurysms. Seventeen months later, arteriography and two-dimensional echocardiography demonstrated regression of the aneurysms. This case provides evidence that regression of aneurysms can occur in mucocutaneous lymph node syndrome.