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A 26-year-old woman was admitted to our hospital because of abdominal mass. She became ileus and an emergency operation was consequently performed. A histological examination of the abdominal tumor indicated proliferation of undifferentiated lymphoblasts with intermingled histiocytes so called "starry sky appearance". The diagnosis was Burkitt's lymphoma. On the 4th post-operative day, a cardiac tamponade became evident. The pericardial effusion contained many lymphoblasts and the diagnosis was pericarditis due to the invasion of lymphoma cells. The pericarditis was successfully treated by infusion of doxycycline into the pericardial space following drainage. The patient responded to systemic chemotherapy with complete remission. 7 courses of systemic chemotherapy along with intrathecal infusions for CNS prophylaxis were subsequently carried out. A state of complete remission has continued for more than 13 months. Cardiac tamponade accompanied by Burkitt's lymphoma is quite rare and has not ever been reported in Japan in our knowledge. The efficacy of surgical treatment before systemic chemotherapy and the series of intrathecal infusions for CNS prophylaxis was demonstrated in this case.

Fifteen patients (8 male and 7 female) with multiple myeloma, who were admitted to our hospital between July 1986 and August 1988 and suffering from pain and hypercalcemia, were treated with synthetic calcitonin derivative (elcatonin: ECT). ECT was administered intravenously at a dose of 10-640 units twice daily. Seven patients were treated with ECT (ECT group), and eight patients received combination treatment with ECT and other form of chemotherapy (combination group). With regard to the pain score (PS), significant analgesic effects in both groups were observed during 1-4 week treatments (p less than 0.05). There were no significant differences in PS between two groups. Serum calcium levels in the combination group at 1 and 4 weeks were significantly lower than the initial value (p less than 0.05). Hypocalcemia was not seen in any of the patients. Urinary excretion of calcium at 1 week in ECT group was higher than the initial value (p less than 0.05). The observed toxicities of ECT were slight nausea and vomiting in only 2 patients. These findings suggest that ECT is an useful agent for the treatment of pain and hypercalcemia accompanied with multiple myeloma.

It is well recognized that weight reduction produces the suppression of serum LH but not FSH level in rodents. In order to clarify the mechanism by which the discrepancy between LH and FSH levels is brought about, the influence of weight loss on the pituitary function was explored using female rats. The changes of the pituitary response to GnRH and the basal secretion of gonadotropins with progressive weight loss were investigated by in vitro short-term incubation of the pituitary gland after prolonged weight loss in female Wistar rats. On the first day of diestrous and until day 14 of the diet, GnRH induced LH and FSH release from the pituitary and a decrease in pituitary content of them, but the total amount of gonadotropin in culture medium and pituitary tissue was not affected. On day 30 of the diet, the decrease in pituitary content disappeared. On day 60 LH release disappeared, whereas pituitary FSH and the total amount of gonadotropins were increased by GnRH. Non-stimulated FSH but not LH secretion per mg of pituitary was augmented during dieting. The data indicate that pituitary responsiveness to GnRH and non-stimulated FSH release were modified by weight loss: the LH-releasing action of GnRH was diminished, the gonadotropin-synthesizing action of GnRH was augmented, and non-stimulated FSH release was increased.

Acute myeloblastic leukemia (AML) was diagnosed in a 54-year-old male, a chronic hepatitis B surface antigen (HBsAg) carrier, in June, 1983. Prompt remission was achieved, and maintenance and intensification chemotherapy were given for five years. He was readmitted in March, 1988 because of a mass in the liver and was diagnosed as having hepatocellular carcinoma (HCC). Curative right segmentectomy was performed in May, 1988. In December, 1988, transitional cell carcinoma of the bladder was discovered, and resected transurethrally. These secondary neoplasms, HCC and bladder cancer, were thought to be associated with the long-term chemotherapy given for the AML.

Two consecutive pregnancies were induced in three hyperprolactinemic primary infertile patients bearing intrasellar microadenoma without visual disturbance. Pretreatment prolactin levels, 224 -496ng/ml, were normalized by 10-22.5mg/day of bromocriptine and the initial conceptions occurred. No abnormal sign due to pituitary enlargement was detected throughout the period of gestation and they delivered single full-term babies. Since no significant change was observed in puerperium, it was decided to give the second bromocriptine therapy. The prolactin levels, 80-190ng/ml, measured before the second therapy were apparently lower than those seen prior to the first therapy and the minimum effective dose used to induce the second pregnancy (5-7.5mg/day) was identical to 1/3-1/2 of the first one. The course of the second pregnancy of each case was also uneventful and the babies were all normal and mature. The magnitude of the rise in the prolactin level during the second pregnancy was smaller than that observed during the first pregnancy. The present longitudinal study throughout two consecutive pregnancies in three cases indicates that resolution of prolactinoma was resulted in some extent after withdrawal of stimulative factors associated with pregnancy. Hence, hyperprolactinemic infertile cases with intrasellar microadenoma can be subjected to bromocriptine therapies inducing consecutive pregnancies under intensive follow-up.

It has been noticed that hyperprolactinemia can cause luteal insufficiency as well as anovulation in women. In order to explore the mechanism underlying this disorder, hyperprolactinemia was induced in baboons (Papio cynocephalus) by daily administration of sulpiride during follicular and early luteal phases. In hyperprolactinemic baboons, the plasma progesterone level was suppressed without notable changes in plasma estradiol, LH and FSH levels. When corpora lutea from these baboons were examined in vitro to investigate their ability to convert 14C-pregnenolone into various steroids, there was progressive inhibition of steroid metabolism related to the plasma levels of prolactin. These findings strongly suggest, although do not actually prove, that an elevated level of prolactin could directly impair luteal function by adversely affecting 3 beta-hydroxysteroid dehydrogenase activity.

Herpes Zoster is a viral disease of the skin and mucosa characterized by grouped vesicula eruptions and neuralgic pain along a peripheral nerve. A case of Herpes Zoster in the right region along the second and third trigeminal nerve branches of a 24-year-old male was reported. The first disorder appeared as a grouped vesicular eruption in the center of the lower lip. This was followed by a cutaneous lesion in the area of the right second trigeminal nerve branch. From the first day of hospitalization, the patient began receiving a daily dose of 2500mg of immunoglobulin. The administration of immunoglobulin, cured the oral and cutaneous lesion.

A method to eliminate the anti-M antibody from maternal circulation was employed in a patient who had four stillbirths caused by MN type incompatibility, and who developed severe post-transfusion hepatitis after plasmapheresis. In this method, the patient's plasma was incubated with OM positive packed red cells to absorb the anti-M antibody and then reinfused. The elevation of titer in maternal blood was prevented, and the ODD-450 values fluctuated in the upper-mid zone of Liley's graph. A viable immature anemic newborn was delivered after C-section in 33 weeks' gestation. As the newly developed antibody elimination therapy physiologically removed the antibody faster than it could accumulate, it contributes to prolonging the intrauterine life span of the fetus. Since the anti-D antibody is also eliminated by the same principle, this procedure seems to be a promising approach for the treatment of the fetal hemolysis due to iso-immunizations.

Plasma hormonal changes were analysed in patients with hyperprolactinemia who conceived following Bromocriptine therapy. Following the administration of HMG-HCG and Bromocriptine, serial plasma samples were collected from the cases. Plasma levels of FSH, LH, prolactin (PRL), estrone (E1), estradiol (E2), 17-hydroxyprogesterone (17-P), 20 alpha-dihydroprogesterone (20 alpha-P), progesterone (P) were determined simultaneously using specific radioimmunoassays. Pretreatment PRL levels, 180--420 ng/ml, were normalized by 7.5--12.5 mg/day of Bromocriptine treatment causing a rapid decrease in plasma PRL, reaching a plateau within several days. The first LH surge at midcycle after the start of the Bromocriptine treatment was established at 10--50 days. In the patients the first mid-cycle LH surge was observed, but the luteal phase was definitely short, as demonstrated by plasma progestins levels. The results from the present longitudinal studies on hyperprolactinemia revealed characteristic changes accompanied by the restoration of the hypothalamic-pituitary-ovarian function during the treatment period.

Proline-rich protein (PRP) is a plasma protein with a high proportion of proline residues and possessing lipid-binding properties. In order to clarify its structure, a human liver cDNA library was screened using anti-PRP antiserum. Several overlapping phage cDNA clones were isolated and the total nucleotide sequence of the cDNA, 2178 bp in length, was analyzed. The amino acid composition of PRP deduced from the cDNA was essentially the same as that reported for PRP. In a homology search, the cDNA sequence was almost completely the same as the previously reported cDNA sequence of C4b-binding protein. Furthermore, the reported molecular weights of the two proteins under both reduced and unreduced conditions were quite alike. These findings indicate that PRP is identical with C4bp.

We investigated the influence of chronic (27-65 days) sulpiride-induced hyperprolactinemia on the menstrual cycles of four normal women. The hyperprolactinemia (206.4 ng/mL, the average of the mean values of each subject obtained by sulpiride treatment) suppressed the LH surge and the secretion of plasma estradiol-17 beta and progesterone to their basal levels. The results suggest that the endocrine changes in normal women with sulpiride-induced hyperprolactinemia are similar to those in women with spontaneous hyperprolactinemia. Sulpiride-induced hyperprolactinemia may be useful as a model for studying spontaneous hyperprolactinemia.

We report fatal transfusion-associated graft-versus-host disease (GVHD) in a patient who was not severely immunosuppressed. A 58-year-old man received 800 ml of fresh whole blood from his son and an unrelated volunteer donor during open heart surgery. On the 10th day after the operation, he suddenly had a high fever, followed by generalized skin rash and liver dysfunction. Pancytopenia due to bone marrow aplasia developed a week later. A skin biopsy revealed a cutaneous lesion highly compatible with acute GVHD. The patient did not respond to high-dose methylprednisolone therapy, and died of multiple organ failure on the 18th day after the operation.

The influence of sulpiride-induced hyperprolactinemia on the hypothalamic-pituitary-ovarian function of the baboon (Papio cynocephalus) was investigated. Plasma levels of prolactin, LH, FSH, estrone, estradiol, 17-hydroxyprogesterone, progesterone and 20 alpha-dihydroprogesterone in control and consecutive treatment cycles (sulpiride i.m. injections 100 mg/day) were determined serially. The hormonal changes indicate that the ovary is the most sensitive site to the direct inhibitory action of sulpiride-induced hyperprolactinemia.

A study was made of formation of the pool of sex steroid hormones and their precursors in the blood plasma of male Paio hamadryas. Cannulation and simultaneous recovery of the blood from the adrenal, testicular, left iliac veins and the aorta were carried out under nembutal anesthesia. Thirteen steroid hormones and their precursors were determined by the radioimmunological method in all the blood portions. Steroid function was tested on columns with celite. Pregnenolone, 17alpha-oxypregnenolone, and 17alpha-oxyprogesterone were secreted chiefly by the adrenal glands. Dihydroepiandrosterone was produced by the adrenal glands and utilized by the testes. Androstendion and dihydrotestosterone were mostly of adrenal, and testosterone--testicular origin. Estron is secreted by the adrenal glands only, whereas estradiol is produced by the testes in larger quantities than by the adrenal glands. The sulfate forms of pregnenolone and dihydroepiandrosterone are produced chiefly by the adrenal glands.

Effects of open-heart surgery on renal function were studied in 38 patients who had uneventful postoperative course with no sign of acute renal failure. Of these, 19 underwent aorto-coronary bypass grafting (Group 1) and 19 underwent valve replacement (Group 2). During cardiopulmonary bypass (CPB), renal plasma flow (RPF) and glomerular filtration rate (GFR) significantly decreased in both groups as compared to the preoperative values. The decreased GFR remained significantly low on the day of operation in both groups and returned to the preoperative level on the 1st postoperative day (POD) in group 1 and on the 3rd POD in group 2. On the other hand, plasma antidiuretic hormone (ADH) level markedly increased during CPB and remained significantly higher than the preoperative level through the 1st POD. Despite the decreased GFR and increased ADH, however, urinary flow markedly increased during CPB in both groups and remained at significantly higher level than the preoperative values through the 3rd POD in group 1 and through the 5th POD in group 2. Fractional excretion of sodium significantly increased during CPB in both groups and remained high through the 1st POD in group 1 and through the 3rd POD in group 2. These data demonstrate that the renal function of urine concentration is disturbed in the early phase following open-heart surgery even in the patients who have uneventful postoperative course.

Acute myeloblastic leukemia (AML) was diagnosed in a 54-year-old male who had been known to carry a chronic hepatitis B surface antigen (HBsAg) from June, 1983. Prompt remission was achieved with combination chemotherapy of BHAC-DMP. Follow-up maintenance and an intensification of this chemotherapy had been given for five years. He was readmitted to our hospital in March, 1988 because a mass was detected in the right lobe of the liver by ultrasonography. His serum alpha fetoprotein (AFP) level was found to be 180.1 ng/ml, and was diagnosed as having a hepatocellular carcinoma though there was no evidence of liver cirrhosis. A curative right hepatectomy was performed in May, 1988 after transcatheter arterial embolization and portal embolization. After resection of the tumor, the AFP level decreased to 10.7 ng/ml and no HbsAg was detected in the serum.

To examine androgenic potential of polycystic ovaries (PCO), slices of follicular and stromal tissues from the same ovary obtained by wedge resection from two markedly, two moderately and one slightly enlarged PCO were incubated separately with [1-14C] acetate. Incorporation into progestins, androgens and estrogens was assessed by reverse dilution technique with recrystallization to constant specific activity. Although the greatest incorporation into androstenedione with much lesser incorporation into testosterone and dehydroepiandrosterone was observed with all the five follicles, the amount of incorporation into the three steroids increased gradedly with histologically defined magnitude of thecal cell hyperplasia in atretic follicles. Only the stromal tissues from two markedly enlarged PCO produced androgens with a similar pattern of 14C distribution among the steroids, thereby incorporation into the three androgens remaining 5.5% or less of that by the follicles from the same ovary. Preoperative levels of plasma androstenedione and urinary 17-ketosteroids were shown to increase in four patients with PCO containing atretic follicles with thecal cell hyperplasia, but not in one patient with slightly enlarged PCO containing atretic follicles without thecal cell hyperplasia. It is inferred that atretic follicles with thecal cell hyperplasia is a significant source of androgen overproduction by PCO.

Twelve-week-old female SD rats were restricted to an 8 g/day feed intake for 2 months followed by feeding ad libitum for 3 weeks. Feed restriction resulted in weight loss and constant diestrous. A persistent increase in the hypothalamic GnRH content was observed during the underfed period. Serum LH and PRL levels dropped throughout the period but the initial reduction in the serum FSH level was observed on the 60th day. The reductions in the pituitary content of these hormones were observed on the 30th day. The decrease in the serum and ovarian E2 levels were detected on the 14th day. Anterior pituitary showed a significant response to GnRH + TRH during the course, and the relative increases in LH, FSH and PRL were greater than those in the pretreatment rats. In the course of refeeding, the body weight returned to the control level and regular estrous cycles were reestablished on the 15th and 21st day, respectively. Elevated hypothalamic GnRH content returned to the control level on the 16th day. The changes in the pituitary-ovarian axis were prompt rebound rises in serum FSH and PRL levels and pituitary FSH content, delayed restoration of serum and pituitary LH levels and serum and ovarian E2 levels, and a marked increase in the serum and ovarian progesterone levels on the 16th day. The relative increases in FSH and PRL after GnRH + TRH injection were smaller than those in the underfed period.(ABSTRACT TRUNCATED AT 250 WORDS)

A radioimmunoassay method has been developed for the simultaneous determination of pregnenolone, pregnenolone sulfate, dehydroepiandrosterone(DHA) and dehydroepiandrosterone sulfate (DHA sulfate). The method consists of the following procedures: 1) ether extraction of unconjugated compounds, 2) extraction of sulfates fromaqueous residue with ethyl acetate, 3) solvolysis with sulfuric acid at 40 degree C for 60 minutes, 4) celite column chromatography to separate individual compounds, 5) radioimmunoassay. Efficiencies of solvolysis for pregnenolone sulfate and DHA sulfate are 94 and 80%, Precision and accuracy studies have shown that the assays of sulfates as well as unconjugates are reproducible and accurate. Specificity was ascertained by parallelism and linearity studies. No interfering substance was detected in appreciable quantity. Plasma levels of these four compounds were determined in specimens obtained from 15 normally ovulating women. To represent the whole menstrual cycle, samples were taken 8 days before LH peak (LH-8), the day of LH peak (LH = O) and 8 days after LG peak (LH+8). Plasma contents of these compounds (geometric mean in ng/ml and 95% confidence limits in parentheses) are as follows: pregnenolone, LH-8: 1.33 (1.02-1.74), LH = 0: 1.45 (1.22-1.72), LH+8: 1.88(1.70-2.21); pregnenolone sulfate, LH-8: 70.0 (55.9-89.2), LH = 0 57.5 (40.0-82.7), LH+8: 102 (81.5-129); DHA, LH-8: 5.38 (3.90-7.43), LH = 0: 4.90 (3.58-6.79), LH+8: 4.58 (3.12-6.83), DHA sulfate, LH-8: 1480 (1110-1980), LH = 0: 1570 (1150-2140), LH+8: 1590 (1150-2190). Both pregnenolone and pregnenolone sulfate levels of 8 days after LH peak are significantly higher than those of other two days. Conversely, plasma DHA and DHA sulfate levels fluctuate over wide range with no consistent trend.

Measurement of bone mineral content (BMC), intestinal 47Ca absorption, and calcium regulating hormones and sex steroids in serum were performed on 32 healthy aged subjects and 26 control young subjects. In BMC, there was a progressive fall after age 40, with the rate of decrease being greater in women than in men. A significant correlation was observed between BMC and testosterone in the men and between estrogens and BMC in the women, suggesting the possible importance of testosterone in men and estrogens in women in maintaining bone mass. Plasma PTH showed no change with age. However, the reserve capacity of the parathyroid was significantly reduced in the aged women. Serum levels of ionized calcium were low in aged subjects, indicating a possible alteration with age in the feedback control between ionized calcium levels and parathyroid hormone secretion. C-cell funtion was also decreased with age. Plasma 1,25-(OH)2D and 47Ca absorption tended to decrease with age. Age-related bone loss could be a reflection of the interaction of these hormonal imbalance occurring with age.

1. Systematic exploration throughout the deep cerebellar nuclei and white matter disclosed that the region from which saccadic eye movements (saccades) were evoked with weak currents (less than 10 microA) was confined to the fastigial nucleus and the adjacent white matter. 2. When an electrode for stimulation was advanced in the cerebellum, saccades were evoked in the direction of the stimulated side (ipsilateral saccades) as it entered the low-threshold region. In some tracks, particularly when the electrode was advanced in the medial portion of the fastigial nucleus, the direction of the evoked saccades changed from the ipsilateral to the contralateral. 3. The mappings with microstimulation disclosed that the ipsilateral saccades were elicited from a relatively wide region that included almost the full extent of the fastigial nucleus. The low-threshold region continued in the white matter caudally into vermal lobule VII and rostrally into the dorsal aspect of the brachium conjunctivum. On the other hand, the contralateral saccades were evoked from a relatively circumscribed region in the ventromedial portion of the fastigial nucleus. 4. The reversal in the direction of the horizontal component occurred always in a narrow zone in the core of the fastigial nucleus. The caudal part of this zone coincided with an ellipsoidal region where anterogradely labeled axons of the Purkinje cells terminated when HRP was injected into vermal lobule VII. 5. When bicuculline (0.2-1 microgram) was injected in the ellipsoidal region, the ipsilateral saccades evoked from the dorsocaudal aspect of the region were suppressed for several hours. On the other hand, the contralateral saccades evoked from the ventromedial portion of the fastigial nucleus were either unchanged or enhanced. 6. Because the ipsilateral saccades were suppressed by bicuculline, they were most probably evoked by stimulation of the presynaptic component of gamma-amino-butyric acid-(GABA) mediated synapses, namely the axons of Purkinje cells. 7. Because stimulation of the presynaptic component of the inhibitory synapses evoked ipsilateral saccades, activation of the postsynaptic component would evoke contralateral saccades. In fact, the distribution of the fastigial sites yielding contralateral saccades coincided with the course of axons of fastigial neurons arising in the ellipsoidal region. It is most likely, therefore, that the contralateral saccades were evoked by stimulation of fastigial neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult baboons (5 males and 5 females) were exposed to immobilization stress by being strapped to a table in a horizontal position for 2 h. In females the experiment was performed during both the follicular and luteal phase. Peripheral blood was withdrawn at frequent intervals, the first sample just before immobilization, and the last one 3 days later. A number of steroids were measured in blood plasma samples by radioimmunoassay (17-hydroxypregnenolone, 17-hydroxyprogesterone, pregnenolone, testosterone, dihydrotestosterone, progesterone, 20alpha-dihydroprogesterone, oestone, oestradiol) or competitive protein binding (cortisol) techniques. The cortisol levels exhibited a marked increase in both sexes. This increase was observed already during the immobilization and lasted for approximately 24 h. A similar, even more pronounced increase was seen in 17-hydroxypregnenolone, 17-hydroxyprogesterone and pregnenolone levels. A marked, long-lasting (72 h) decrease of testosterone and dihydrotestosterone levels was a consistent finding in male baboons. This was not observed in the females which, on the other hand, exhibited a marked decrease (duration 48 h) of progesterone and 20alpha-dihydroprogesterone levels during the luteal phase, and a significant decrease (duration greater than 24 h) of oestradiol and oestrone concentrations during the follicular phase. It is concluded that stress has a marked inhibitory action on gonadal function both in male and female baboons. In females and inhibition of steroidogenetic function is exerted both on the ovarian follicles and on the corpus luteum.

Intravenous GnRH pulsatile infusion therapy (10 micrograms/pulse, 90-min interval) was conducted in an acromegalic patient from whom 2/3 of a GH-producing pituitary macroadenoma had been removed. Before infusion therapy, plasma levels of GH and PRL were 10-20 and 15-25 ng/ml, respectively, while those of LH and FSH were subnormal without intrinsic fluctuations. Ovulation was induced after 13 days of infusion which was terminated on the 23rd day of therapy. Luteal function was supported by hCG (5,000 IU per dose) which was given 4 times from the 23rd to the 31st day of the treatment cycle. Triplet pregnancy was diagnosed ultrasonographically within 7 weeks of gestation. Although GH and PRL levels increased gradually as the gestational period progressed and plasma levels of GH and PRL of 32-55 and 30-67 ng/ml, respectively, were detected after 30 weeks of gestation, neither adverse signs related to the enlargement of the residual pituitary tumor nor manifestation of acromegaly was observed. The immunoreactive somatomedin-C levels during this period were not greater than those in normal pregnant women. Caesarean section was performed at 34 weeks and 3 normal healthy infants were delivered. Detailed analyses of hormonal changes throughout the period of GnRH pulsatile infusion and subsequent luteal phase revealed that the triplet pregnancy had been induced by the GnRH therapy itself and that hCG stimulation did not play any critical role. The residual tumor mass secreted increasing amounts of GH during the latter period of pregnancy but the somatomedin-C levels were not associated with this elevation. Therefore, the clinical as well as the hormonal findings strongly suggested that the GH secreted in increasingly large amounts by the residual tumor mass during pregnancy was defective in certain biological properties.

Morphological and endocrinological studies were performed on a 19-year-old case of an arrhenoblastoma with marked virilization. The tumor was an intermediate type of Meyer's classification. Histochemically, 3 beta-HSD and G-6-PDH activities were demonstrated in Leydig cells. These cells also had ultrastructures typical of steroid-producing cells. Basal blood cells of pregnenolone, dehydroepiandrosterone, testosterone (T), androstenedione (A), progesterone, estradiol, estrone, LH, and FSH were determined pre- and postoperatively. T and A showed a very high level preoperatively, and were markedly decreased immediately after removal of the tumor. Stimulation of tumor cells by HMG-HCG did not show any significant changes in their main products of T and A. These findings suggest that Leydig cells of the present tumor produced mainly A and T independently on gonadotropins, and these hormones had virilized the patient.

Plasma levels of unconjugated oestrone, oestradiol, oestriol and progesterone were serially studied in six uncomplicated patients in the mid-trimester of pregnancy before and during abortion induced by purely mechanical stretching of the uterus by laminaria and rubber balloon. Variability of these hormonal levels among patients was significant before the treatment. In four cases where the fetus was aborted alive, the plasma value of these hormones remained at a high level during the treatment with the exception of oestriol level in one case. In two early mid-trimester cases the fetus died during the treatment and plasma oestriol dropped significantly, while the level of the other hormones remained raised until fetal delivery. In these two cases the apparent onset of labour was noted before fetal death. It was concluded that the onset and progress of labour by mechanical stretching of the uterus is probably unrelated to the steroid hormones estimated in the present study.

The plasma levels of estradiol and progesterone in 5 mature female Japanese monkeys (Macaca fuscata fuscata) throughout a breeding and nonbreeding season were measured by radioimmunoassay. As the breeding season approached, plasma estradiol levels started to increase and a few elevations were detected. However, neither a plasma progesterone rise nor menstrual bleeding was seen. Menstrual bleeding began in December and recurred regularly 4 or 5 times at 4 week intervals until April. During this period, cyclic estradiol elevations (150-250 pg/ml) and luteal progesterone rises (2.0-5.3 ng/ml) were observed. After the last menstruation in March or April, two animals showed an estradiol elevation, but progesterone levels remained in the basal range and amenorrhea persisted. These data indicated that female Japanese monkeys ovulate 4 or 5 times a year, i.e., their breeding season is definitely defined. The changes of both steroids in transitional periods between nonbreeding and breeding, and breeding and nonbreeding seasons, suggested that some follicle development occurred in these periods. The elucidation of the mechanisms involved in the seasonal variation of reproductive functions in the Japanese monkey may provide useful information concerning some aspects of amenorrhea in human females.

In an attempt to find suitable animal models to aid in the study of the reproductive processes of the human male, plasma levels of unconjugated pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, 20alpha-dihydroprogesterone, 17-hydroxyprogesterone, androstenedione, testosterone, dihydrotestosterone, oestrone and oestradiol were measured in 18 male baboons and 10 male rhesus monkeys and the steroid levels were compared with those previously established in normospermic, middle-aged men. Significant species differences were found with regard to the three delta5-steroids studied; whereas the approximate relationship of pregnenolone to 17-hydroxypregnenolone and dehydroepiandrosterone was 1:2:4 in men, the corresponding relationship was 1:5:30 in rhesus monkeys and 1:10:10 in baboons. Similar levels of 20alpha-dihydroprogesterone were found in the three species. On the other hand, the 17-hydroxyprogesterone levels in baboons were much lower and the levels of androstenedione lower than those found in men and in rhesus monkeys. No species difference was found with regard to circulating testosterone levels. However, both rhesus monkeys and baboons exhibited much higher levels of dihydrostestosterone than did men. Oestrone levels were higher in baboons than in men and oestradiol levels were higher in rhesus monkeys than in men and in baboons. The significant differences in circulating steroid levels suggest that further studies (including i.a. steroid analyses in testicular tissue, seminal plasma and spermatic artery and vein following both stimulation and suppression of testicular endocrine function) are required before preference can be given to any of the two species studied as a suitable animal model for the study of new fertility regulating agents.

A ten-year-old Japanese boy with tricuspid atresia type IB was treated by direct anastomosis from the right atrium (RA) to the right ventricle (RV), entirely with autogenous material. An incision of the RA anterior wall was designed for a flap of RA appendage. A valveless conduit was created, with this flap and a large piece of pericardium. Atrial septal defect (ASD) and ventricular septal defect (VSD) were closed with a patch. Cardiac catheterization and angiocardiography two months postoperatively, showed good results of the surgery.

In control rats, the arsenic level in the spleen and blood cells was 1.59 and 10.79 microgram/g wet tissue, respectively. In the kidney, lung, heart, brain, and hair, the arsenic level was lower than 1.1 microgram/g wet tissue. In rats in which a pellet containing 2 mg of arsenic tsioxide was implanted subcutaneously, the arsenic level in the spleen and blood cells was markedly high for at least 2 months after implantation; after 67 days of implantation, the arsenic level in the spleen and blood cells was 16.79 and 66.34 microgram/g wet tissue, respectively. In the kidney, liver, lung, heart, brain, and hair, the increase in arsenic after implantation was smaller than that in the spleen. In the plasma, arsenic was not detected before and after arsenic implantation. It is concluded that arsenic implanted subcutaneously concentrates in the blood cells, possibly in the red cells, in rats.

To determine the acute and chronic effects of suckling on maternal PRL secretion in monkeys, five mother-infant pairs were studied longitudinally on days 40, 80, 120, and 10 after weaning (day 160). Mothers were chronically cannulated and, during blood collections, wore protective nylon vests with mobile tethers. Studies were undertaken during the day and night with the mother and infant undisturbed, during the daytime, before and after the removal of the infant, and during the day and night before and after the reunion of mother and infant. Maternal PRL levels were significantly (P less than 0.05) higher at night than during the day in undisturbed mother-infant pairs. This nocturnal elevation was probably induced by a more intensive interaction of the mother and infant at night than during the day. Basal PRL concentrations in samples collected during these undisturbed settings significantly (P less than 0.05) declined as the postpartum interval continued. The removal of the infant did not perturb maternal PRL patterns. Typically, after reunion of mother and infant, maternal PRL levels were increased significantly (P less than 0.05), reaching maximal levels approximately 2 h after reunion. If PRL secretion, induced by the suckling stimulus, is instrumental in sustaining puerperal infertility, then the increased secretion of PRL that occurs at night during the protracted interval of intense mother-infant interaction may be of particular significance in inhibition of the hypothalamic-pituitary-ovarian axis.

Intravaginal treatment with a PGE-1 analogue (ONO-802) resulted in strong uterine contractions with a high frequency which lasted for more than 3 h. When 20-50 microgram ONO-802/kg were administered intravaginally 5 times every 3 h in 5 pregnant animals, vaginal bleeding started by 6 h and abortion occurred by 26 h after the initial treatment. There were no significant side effects. Plasma levels of steroid hormones, especially progesterone and 20alpha-dihydroprogesterone, fluctuated initially and then finally dropped to undetectable levels within 24 h.

The efficacy of every-other-day gonadotropin-releasing hormone administration was investigated in clomiphene-human chorionic gonadotropin (hCG) resistant, anovulatory women with hypogonadotropism or normogonadotropism. One hundred micrograms of gonadotropin-releasing hormone was injected intramuscularly three times a week for four weeks (one course). Ten of 11 hypogonadotropic patients responded to clomiphene or clomiphene-hCG after one to three courses of gonadotropin-releasing hormone treatment. Once the patients were converted to clomiphene responsiveness, ovulatory response continued without additional treatment, and all four patients who desired pregnancy conceived. Among eight normogonadotropic women, four with amenorrhea of one year or less became clomiphene-hCG responders after one or two courses of gonadotropin-releasing hormone treatment. They were subsequently treated with gonadotropin-releasing hormone after every one or two ovulatory cycles. One of the four women who desired to be pregnant conceived. We conclude that intramuscular gonadotropin-releasing hormone treatment is effective in inducing responsiveness to clomiphene, especially in hypogonadotropic anovulatory women. In normogonadotropic women, gonadotropin-releasing hormone treatment may be useful in those who have been amenorrheic for less than a year.

In an attempt to analyze the multiple changes and interactions in circulating steroid levels in the peri-ovulatory and peri-menstrual periods, the plasma levels of immunoreactive luteinizing hormone (LH), progesterone and unconjugated pregnenolone, dehydroepiandrosterone, testosterone, oestradiol and oestrone were assayed daily during a complete cycle in 17 normally menstruating women. In 14 of the 17 subjects studied androstenedione and unconjugated dihydrotestosterone were also estimated. The day of the LH-peak and the first day of menstruation, respectively, were used to synchronize the peri-ovulatory and peri-menstrual plasma levels of the various steroids. With the exception of dehydroepiandrosterone and dihydrotestosterone, the plasma levels of all steroids exhibited significant, but different changes during the cycle. Testosterone levels showed a slight but significant increase around the LH-peak, whereas the levels of pregnenolone and androstenedione were higher in the post-ovulatory than in the pre-ovulation periods. The levels of oestradiol and oestrone, as well as the ratios of oestradiol to oestrone gradually increased from the low values observed in the early proliferative phase to pre-ovulatory peak values. The relationship between peaks of oestradiol and oestrone and that of LH exhibited great individual variation. The same was true for the individual oestradiol to oestrone ratios. The combination of several steroidal signals did not improve the predictive value of the analyses. However, an increase of individual progesterone values by at least 0.35 ng/ml from the day preceding the LH-peak to the day of the LH-peak was observed in 13 of the 17 subjects. It is suggested that for the early detection of the LH surge and prediction of the subsequent ovulation daily assays of plasma progesterone are of more value than the assay of the other steroids investigated.