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Biomedical subjects

H Suginami

Publications and source records attributed to H Suginami.

At least 37 records · Page 2Linked to original sources

The expression of c-kit protein in human adult and fetal tissues.

The c-kit proto-oncogene encodes a tyrosine kinase receptor and is allelic with the dominant white-spotting (W) locus of the mouse. In this study we investigated the expression of human c-kit protein in various adult and fetal human tissues immunohistochemically using anti-human c-kit monoclonal antibody. To discriminate c-kit+ cells from mast cells expressing c-kit, mast cells were identified by staining with Toluidine blue. In oogonia, spermatogonia and skin melanocytes of the fetus and in oocytes of adult ovary, c-kit expression was detected. In adult uterus, c-kit+ cells were widely distributed in the basal layer of the endometrium, myometrium and cervix, the number and distribution being almost identical to those of mast cells. In fetal uterus, c-kit+ non-mast cells clustered beneath the epithelium and a few mast cells were observed in the myometrium and subserosal layer. In both adult and fetus, c-kit+ non-mast cells were detected within smooth muscle layers of the intestine, colon and oesophagus, while mast cells were observed in the mucosal and submucosal layers of these organs. In contrast to mice, no expression of c-kit protein was detected in the human placenta and decidua. Thus, the distribution of c-kit+ cells in various tissues is similar but not identical between adult and fetus and between human and mouse.

Adult↗

Human leukocyte antigen-DR is a differentiation antigen for human granulosa cells.

We raised a murine monoclonal antibody, OG-3, which reacts with human granulosa cells. Immunohistologically, OG-3 antigen was weakly expressed on the granulosa cells of some growing and atretic follicles, but not on those of preovulatory follicles. After ovulation, the antigen expression rapidly increased on granulosa cells during corpus luteum formation. The antigen expression on granulosa/large luteal cells decreased in the mid-luteal phase, but increased again in the late luteal phase. In early pregnancy, OG-3 antigen expression on large luteal cells increased after 7 wk of gestation. The OG-3 antigen distribution in various organs resembled that of human leukocyte antigen (HLA) class II molecules. An HLA-class II-positive human B cell line (AKIBA) and a murine L-cell transfectant expressing HLA-DR antigen were positive for OG-3 antigen, whereas an HLA-class II-negative human T-cell line and L-cell transfectants expressing HLA-DP and DQ antigens were negative. The molecular mass of OG-3 antigen purified from AKIBA cells was 32-35 kDa. The staining profiles in ovaries with anti-HLA-DR or anti-HLA-class II antibodies were similar to that with OG-3. These results indicate that OG-3 antigen is identical to HLA-DR, and that HLA-DR is a differentiation antigen for human granulosa cells.

Adult↗

Endocrine pathophysiology of luteal phase deficiency as assessed by GnRH/TRH stimulation tests performed in the early follicular and midluteal phases of the menstrual cycle.

To investigate endocrine pathophysiology of luteal phase deficiency (LPD), GnRH/TRH stimulation tests were performed in the early follicular (EFP) and midluteal phases (MLP) of the menstrual cycle in 52 infertile women with a history of short luteal phase, in whom pituitary responsiveness to GnRH/TRH and steroidogenic competency of the corpus luteum were analyzed. Twelve women with either elevated basal-LH or exaggerated PRL response to GnRH/TRH in EFP were eliminated, and the remaining 40 women were studied. Basal-FSH in EFP inversely correlated with steroidogenic parameters in MLP, indicating that compromised folliculogenesis causes LPD. In a fraction of LPD women, decreased basal-LH in MLP was associated with decreased basal-progesterone (p), in spite of normal steroidogenic potential of the corpus luteum, suggesting that aberrant LH secretion is another progenitor of LPD. The other group of LPD women showed shortening of high phase period and/or extravagant discrepancy in endometrial dating without apparent abnormal endocrine parameters, suggesting that unknown factors are involved in establishment of LPD. From the diagnostic point of view, they were discriminated into three groups, normal, incomplete LPD and complete LPD groups, with a modified classification of LPD; 1) shortening of high phase period < 11 days, 2) delay in histological to chronological dating of the endometrium > 2 days, and 3) decreased max-P in MLP < 10 ng/ml. Normal (n = 14) and complete LPD (n = 7) groups consisted of women having all the criteria of classification within and out of the cut-off values, respectively. The remainders were enrolled into incomplete LPD group (n = 19). Complete LPD group mainly consisted of women having compromised folliculogenesis as a cause of LPD. In contrast, incomplete LPD group appeared a mixture of heterogeneous populations as to the genesis of LPD. GnRH/TSH stimulation test, especially when performed in MLP, would unveil endocrine pathophysiology of LPD and provide an accurate standard for diagnosis of LPD.

Adult↗

Immunohistochemical localization of androgen receptor in the human ovary throughout the menstrual cycle in relation to oestrogen and progesterone receptor expression.

In order to elucidate the role of androgen receptors (AR) in human ovaries, we examined their immunohistochemical localization, in comparison with oestrogen receptors (ER) and progesterone receptors (PR), at various stages of the menstrual cycle and follicular development. Primordial and primary follicles did not express AR. In granulosa and thecal cells of secondary follicles there was weak nuclear staining for AR. Granulosa cells of dominant follicles showed moderate nuclear staining for AR, which was stronger than that in thecal cells. In the luteal phase, the staining intensity for AR was strongest in the early luteal phase just after ovulation and declined gradually thereafter. Thecal cells of atretic follicles showed moderate nuclear staining for AR, which was a little stronger than that in dominant follicles. There was weak nuclear staining for AR in stromal cells surrounding follicles. Though there was variation in the staining intensity, AR were present at almost all stages of the menstrual cycle. There is a possibility that androgens, mediated by AR, may play an essential role in follicular growth and maturation, atresia and luteinization as autocrine or paracrine agents.

Adult↗

A reappraisal of the coelomic metaplasia theory by reviewing endometriosis occurring in unusual sites and instances.

Endometriosis occurring in unusual sites and instances was reviewed for the purpose of exploring the pathogenesis of the disease. Endometriosis is frequently observed in the pelves of menstruating women. It occurs in teenagers even before menarche, in women who have never menstruated, and in postmenopausal women. It affects not only the pelvic organs but also the right-sided thoracic organs and rarely the extremities. It occurs in men who are castrated and treated with estrogen. The affected sites in both common and uncommon endometriosis include cells arising from the coelomic membrane and sites exposed to metaplasia-inducing substances such as estrogen and unknown factors liberated from the degenerating endometrium. This appears to strengthen the coelomic metaplasia theory, although additional basic and experimental data must still be accumulated to confirm this theory.

Child↗

Pregnancy suppression by a platelet activating factor antagonist, ONO-6240, in mice.

Mouse embryos produce an embryo-derived platelet activating factor (EDPAF) during their early developmental stages. The present study was aimed at investigating the physiological significance of EDPAF by using a specific PAF antagonist, ONO-6240. EDPAF-induced platelet decrease was antagonized by ONO-6240 in a dose-dependent manner, although this alone did not affect circulating platelet concentrations. ONO-6240, when administered to maternal mice, increased the proportion of mice conceiving small litter sizes, whereas it did not affect in vivo or in vitro development of embryos. EDPAF was suggested to play an important role in establishing pregnancy in mice by promoting implantation.

Animals↗

Pregnancy suppression by a structurally related antagonist for platelet activating factor, CV-6209, in mice.

The effects of CV-6209, a structurally related antagonist for platelet activating factor (PAF), on pregnancy were investigated in mice, so that the physiologic significance of PAF production by and secretion from preimplantation embryos could be elucidated. When it was repeatedly administered to pregnant mice during days 1-6 of pregnancy, CV-6209 prevented preimplantation thrombocytopenia and reduced the number of implantation sites dose-dependently, CV-6209 suppression of pregnancy was eliminated by concomitant administrations of PAF. When it was administered on various fractional days of pregnancy, CV-6209 suppressed pregnancy most effectively in mice treated during days 4-5 of pregnancy, the days of implantation. CV-6209 treatment exhibited no apparent effect on embryonic development. Implantation was suppressed when day 4 embryos from saline-treated donor mice were transferred in utero to CV-6209-treated recipient mice. Once implanted, however, their in utero growth was normal. The results indicate that PAF is prerequisite to pregnancy by promoting embryonic implantation.

Animals↗

Intravenous leiomyomatosis with cardiac extension: successful surgical management and histopathologic study.

A case of intravenous leiomyomatosis with cardiac extension was treated successfully with a two-stage operation: resection of the intracardiac and intracaval mass for the first stage and total hysterectomy with bilateral salpingo-oophorectomy for the second. Tumors were located either within or in continuity to dilated uterine veins. A leiomyomatous protrusion of the wall of a small uterine vein was found in two remote sections. The involved veins were located alone in the layer of apparently normal uterine smooth muscles. The findings suggest that intravenous leiomyomatosis originates from the smooth-muscle component of uterine veins.

Aged↗

[Changes in plasma estradiol, progesterone and LH level in the menstrual cycle of the adult female Japanese monkey during the mating season].

Adult 15 female Japanese monkeys showing regular menstrual cycles were subjected to the daily blood sampling for the measurement of estradiol (E2), progesterone (P) and biological LH in the mating season. Monkeys were maintained under controlled conditions in a standardized environment. Of the 35 cycles observed, 18 (51.4%) were estimated as anovulatory cycles and 17 (48.6%) were ovulatory cycles. The anovulatory cycles were classified into three types according to the peak level of E2 (Type I: E2 less than 50 pg/ml 3 cycles, Type II: E2 less than 170 pg/ml 7 cycles, Type III: E2 greater than 170 pg/ml 8 cycles). The ovulatory cycles were classified into two Types according to the peak level of P (Type IV: P less than 5.0 ng/ml 5 cycles, Tyep V: P greater than 5.0 ng/ml 12 cycles). The menstrual cycle was 27.5 +/- 7.8 days. The differences between mid cycle LH surge and P level in Type IV and in Type V were statistically significant. It was revealed that female Japanese monkeys kept under controlled condition in the mating season showed high incidence of various types of anovulatory cycles and that the ovulatory cycles with low P elevation in the mid luteal phase showed low LH and P secretions on the mid cycle date.

Animals↗

[Qualitative and quantitative changes of luteinizing hormone (LH) in the pituitary glands in female Japanese monkeys (Macaca fuscata) during the menstrual cycle and after castration].

The present study was designed to investigate qualitative and quantitative changes in luteinizing hormone (LH) in the pituitary glands of female Japanese monkeys (Macaca fuscata) during the menstrual cycle and after castration. The pituitary glands were removed from 10 intact cycling Japanese monkeys and 3 castrated ones: The former sacrificed in the early, late follicular phase, and mid luteal phase, and the latter 8 weeks after castration. All 13 pituitary glands were fractionated by isoelectrofocusing (IEF). The mid cycle peaks of estradiol (E2) and bioactive LH occurred simultaneously in 11 out of 13 monkeys. No animals showed luteal phase peaks in the plasma E2 concentration. Bioactive LH content (IU/mg wet weight) in the pituitary gland was significantly correlated with plasma E2 levels in the cycling monkeys (R2 = 0.974) and it was the highest in monkeys in the late follicular phase. Bioactive LH in the pituitary gland was separated into 6 distinct species in terms of pI values by IEF; A(9.31 +/- 0.19), B(8.88 +/- 0.17), C(8.36 +/- 0.17), D(7.92 +/- 0.18), E(7.32 +/- 0.16) and F(acidic LH). Among alkaline LH species, the most predominant ones were Fractions B, C and D in the early follicular phase, Fraction A followed by B in the late follicular phase and Fraction B followed by C in the mid luteal phase. The neutral and acidic LH (Fraction E and F) was increased more in the early follicular phase and in the castrates. In conclusion, LH species separated by IEF may correspond to the stage of molecular maturation of pituitary LH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An ovum capture inhibitor (OCI) in endometriosis peritoneal fluid: an OCI-related membrane responsible for fimbrial failure of ovum capture.

The present study was conducted to assess the mechanism of in vitro interference with fimbrial ovum capture by the ovum capture inhibitor (OCI) which we have recently demonstrated in endometriosis peritoneal fluid (PF). A golden hamster oviduct exposed to either endometriosis or nonendometriosis PF for 20 minutes at 37 degrees C was examined by scanning electron microscopy. Exposure of the oviduct to endometriosis PF reduced fimbrial activity of ovum capture and developed an OCI-related membrane on the fimbria, by which fimbrial cilia were completely concealed. This was not the case for nonendometriosis PF. Subsequently, an oviduct having been exposed to endometriosis PF was retrogradely flushed, by which the OCI-related membrane was ballooned and removed. The flushed oviduct resumed its activity of ovum capture. The OCI-related membrane appeared a cause of OCI interference with fimbrial ovum capture by preventing the contact between the fimbrial cilia and the cumulus oophorus.

Adult↗

Continuous subcutaneous infusion of human menopausal gonadotropin in anovulatory women with decreased FSH/LH ratio and androgen excess.

Ten women of polycystic ovarian-type (PCO-type) anovulation, having a decreased ratio of FSH to LH and androgen excess, resistant to the previous clomiphene, bromocriptine and/or daily im injections of human menopausal gonadotropine (hMG), were treated with continuous sc infusion of 150 IU/day hMG. The treatment was initiated on cycle day 2-5 and continued until the dominant follicle reached 20 mm or more in diameter, when an im bolus of 10,000 IU human chorionic gonadotropin was given. The treatment elevated the geometric mean of pretreatment serum FSH (8.6 mIU/ml) to 15.9 mIU/ml (p less than 0.001), while serum LH decreased from 29.4 mIU/ml to 20.7 mIU/ml (p less than 0.01). This resulted in a highly significant increase in the FSH/LH ratio from 0.29 to 0.77 (p less than 0.0001). Follicle enlargement was demonstrated in 13 of the 14 treatment cycles, 12 of which were ovulatory. Pregnancy ensued in 4 cases, 1 of which was a quadruplet pregnancy. Continuous infusion of hMG was indicated as an effective way of inducing ovulation in PCO-type anovulation resistant to conventional methods of ovulation induction.

Adult↗

Bromocriptine treatment in anovulation with decreased ratio of follicle stimulating hormone to luteinizing hormone and with hyperandrogenism.

Twenty-six anovulatory women of polycystic ovarian (PCO)-type were treated with bromocriptine (Br) at a daily dose of 5 mg for 2 months. Ovulatory cycles were resumed in 18 (69.2%) women (Br-responders). No difference between pretreatment serum levels of FSH, LH, PRL and estradiol and FSH/LH ratios in Br-responders and nonresponders was observed. The geometric mean of circulating androstenedione (A-dione) in Br-responders (2.58 ng/ml) appeared higher than that in nonresponders (2.11 ng/ml) but was not statistically significant. The geometric mean of dehydroepiandtrosterone sulfate (DHEA-S) in Br-responders (1652 ng/ml) was lower (p less than 0.01) than that in nonresponders (2582 ng/ml). The ratio of DHEA-S to A-dione (D/A ratio) exhibited a highly significant between-group difference (p less than 0.001) (646 and 1222 for Br-responders and nonresponders, respectively). Br-nonresponders with high DHEA-S levels and D/A ratios tended to hyperproduction of adrenal androgen, and Br-responders with high A-dione levels and low D/A ratios to hyperproduction of ovarian androgen. The present study indicates that Br is effective in PCO-type women presumably with ovarian androgen hyperproduction. The efficacy of Br, when applied to PCO-type women, could be predicted with their D/A ratios.

Adult↗

[Transient hyperprolactinemia during ovulation induction with gonadotropin releasing hormone (GnRH) pulsatile administration].

Seven clomiphene-resistant normoprolactinemic anovulatory patients were treated with GnRH pulsatile administration (total 15 treatment cycles). Several problems with GnRH pulse therapy were raised through 6 unsuccessful cases. In 5 cases (10/15 treatment cycles), transient hyperprolactinemia (50-100 ng/ml) appeared immediately after the initiation of the treatment and persisted for 6-10 days. Follicle maturation and ovulation was not induced in these cases. Frequent blood sampling failed to demonstrate GnRH-induced LH secretion in 3 cases. Synchronous secretion of PRL with LH was observed when serum PRL levels were low, but not in situations with elevated serum PRL levels. The lack of GnRH-induced LH secretion indicates the down-regulation of the pituitary with increased frequency of GnRH pulses due to intrinsic and exogenous GnRH. The synchrony of LH and PRL suggests the contribution of GnRH-mediated PRL releasing factor (PRF) through a paracrine system between gonadotrophs and lactotrophs. Transient hyperprolactinemia observed in the current study might be attributable to a relative increase in GnRH to a GnRH-associated peptide (GAP), a constituent of GnRH prohormone and possessing an intrinsic effect of PRL suppression, by exogenously administered GnRH, causing overwhelming superiority of GnRH-mediated PRF. Transient hyperprolactinemia and regulation of the pituitary may hamper ovulation induction with GnRH pulse therapy when applied to cases with intact hypothalamic-pituitary axis.

Anovulation↗

[Ultrasonographic diagnosis of cul-de-sac endometriosis].

Fifty-six women with endometriosis were examined for cul-de-sac endometriosis by ultrasonography and laparoscopy. Ultrasonographic cul-de-sac findings were classified into 3 groups; i.e. Group A (n = 21): no remarkable findings, Group B (n = 16): several nodular hyperechoic or cystic hypoechoic areas, and Group C (n = 19): multiple nodular or cystic areas and/or discontinuation of the contour of the posterior uterine wall. Laparoscopic cul-de-sac findings were classified into 3 groups; i.e. Group alpha (n = 6): no endometriosis, Group beta (n = 28): minimal or mild endometriosis, and Group gamma (n = 22): advanced endometriosis with or without cul-de-sac obliteration. Over-all coincidence of both findings was 50%. The rate of coincidence was significantly higher (p less than 0.05) in Group gamma (15/22) than in Group beta (9/28). This indicates that the diagnosis of minimal or mild cul-de-sac endometriosis by means of ultrasonography is difficult but that ultrasonography might be useful in diagnosing advanced cul-de-sac endometriosis.

Culdoscopy↗