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Biomedical subjects

I Miyakawa

Publications and source records attributed to I Miyakawa.

At least 19 recordsLinked to original sources

Platelet-activating factor stimulates cytokine production by human endometrial stromal cells.

Although preimplantation embryo and decidual cells secrete significant amounts of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF); its precise function in early pregnancy has yet to be established. To investigate the effect of PAF on cytokine synthesis, we measured the cytokine concentration in the culture media of two human cell lines: normal endometrial stromal cells (ESC) and endometrial stromal sarcoma cells (MaMi), following stimulation with a non-metabolized PAF analogue, carbamyl-PAF (C-PAF). Enzyme-linked immunosorbent assays were used to measure five cytokines: interleukin (IL)-6, IL-8, macrophage colony-stimulating factor (M-CSF), macrophage inflammatory protein-1alpha (MIP-1alpha) and tumour necrosis factor-alpha (TNF-alpha). We also evaluated the mRNA expression for IL-6 and IL-8 in ESC after C-PAF stimulation using Northern blot analysis. Non-stimulated ESC and MaMi cells both secreted IL-6, IL-8, and M-CSF, but not MIP-1alpha or TNF-alpha. The concentrations of IL-6, IL-8, M-CSF, MIP-1alpha, and TNF-alpha in the culture media of both cell lines increased in parallel with increasing amounts of C-PAF. C-PAF stimulated IL-6 and IL-8 transcription in ESC. These results suggest that PAF secretion by decidual tissues and developing embryos may induce cytokine synthesis by the ESC, as part of the cytokine network in the feto-maternal unit. An increase in the local cytokine concentration may be an important factor in the maintenance of early stages of gestation.

Adult

Expression of hepatocyte growth factor in cultured human endometrial stromal cells is induced through a protein kinase C-dependent pathway.

To examine the production of hepatocyte growth factor (HGF) by human endometrial stromal cells (ESC) in vitro, concentrations of HGF in the culture media of ESC were measured after the addition of various amounts of 12-O-tetradecanoylphorbol 13-acetate (TPA), forskolin, lipopolysaccharide (LPS), interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha (TNFalpha), interferon-gamma (IFNgamma), or ethynylestradiol-17alpha using an ELISA. The expression of HGF mRNA was also assayed by a reverse transcription-polymerase chain reaction. The concentration of HGF in the culture media of unstimulated ESC was below the detection level of the assay. TPA stimulated the secretion of HGF by ESC in a dose-dependent manner. TPA also induced the transcription of HGF mRNA by ESC. Forskolin, LPS, IL-1beta, IL-6, IL-8, TNFalpha, IFNgamma, or ethynylestradiol-17alpha did not alter HGF mRNA or protein levels. TPA-stimulated production of HGF was partially inhibited by the addition of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine or sphingosine. These results suggest that a protein kinase C-dependent pathway may play an important role in the regulation of HGF production by ESC. HGF secreted by ESC may be involved in the regeneration of the endometrium during the normal menstrual cycle.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Pregnancy-associated osteoporosis with elevated levels of circulating parathyroid hormone-related protein: a report of two cases.

Two lactating women who had complained of back pain developed spontaneous vertebral fractures with low bone mineral density (BMD) several months postpartum. The back pain and biochemical abnormalities presented as hypercalcemia and elevated plasma levels of the parathyroid hormone-related protein (PTH-rP) that returned to normal indices with increasing BMD after weaning. The increased circulating PTH-rP might contribute to the pregnancy-associated osteoporosis in women who probably are already osteopenic.

Absorptiometry, Photon

Remission of idiopathic hypoparathyroidism during lactation: a case report.

A 35-year-old woman with idiopathic hypoparathyroidism achieved a spontaneous remission during lactation even though 1-alpha-hydroxyvitamin D3 therapy was discontinued after delivery. Urinary excretion of cyclic adenosine 3',5'-monophosphate and phosphate was significantly increased during lactation, probably in response to the increased levels of circulating parathyroid hormone-related protein derived from the breast tissue.

Adult

Endometrioid adenocarcinoma arising from adenomyosis.

In spite of many references to carcinoma arising from endometriosis at extrauterine sites, there are few documented cases of carcinoma developing in association with adenomyosis. We present 2 rare cases of adenocarcinoma arising from adenomyosis. The relationship between prior frequent estrogen use and carcinogenesis and the possible effects of chemotherapy and radiation therapy are reviewed.

Adenocarcinoma

Torsion of a functional ovarian cyst in a premenopausal patient receiving tamoxifen.

We report a case of torsion of an ovarian follicular cyst that developed during treatment with tamoxifen for breast cancer. A 40-year-old Japanese woman was admitted complaining of acute lower abdominal pain. Eight months earlier, she had undergone a partial mastectomy and local irradiation for ductal carcinoma of her left breast, estrogen receptor-positive stage I (T(1a) N(1b) M(0)). The administration of tamoxifen, 20 mg/day, and doxifluridine, 600 mg/day, were started immediately postoperatively. Pelvic examination after admission revealed the left ovarian cyst and enlarged uterus. Transvaginal ultrasonography and computed tomography revealed a multilocular cystic mass in the pelvic cavity. The pathological diagnosis of the tumor after total hysterectomy and bilateral salpingo-oophorectomy was a typical follicular cyst with torsion and uterine leiomyoma. This ovarian cyst was believed to have developed during tamoxifen administration.

Adult

Interleukin-1beta and interleukin-8 in cervicovaginal fluid during pregnancy.

OBJECTIVE: We investigated the usefulness of cervicovaginal interleukin-1beta and interleukin-8 levels during pregnancy as markers of preterm and term parturition. STUDY DESIGN: Cervicovaginal fluids were obtained from 119 pregnant women at 24 to 41 weeks' gestation. Cytokine concentrations were measured by enzyme-linked immunoassay. RESULTS: Interleukin-1beta and interleukin-8 concentrations in cervicovaginal fluids obtained from women not in labor increased exponentially as gestational age increased. Interleukin-1beta and interleukin-8 concentrations were significantly correlated. These cytokine concentrations were significantly higher in patients in preterm labor than in patients at preterm not in labor and were significantly higher in women at term in labor than in women at term not in labor. These cytokine levels were significantly correlated with the degree of cervical dilation and tocolytic index. CONCLUSIONS: These findings suggest that cervicovaginal interleukin-1beta and interleukin-8 contribute to term and preterm parturition. Measurement of cervicovaginal concentrations of these cytokines may be clinically useful in patients with threatened premature delivery.

Adult

Effects of interferon-gamma on cytokine production by endometrial stromal cells.

To clarify the role of interferon-gamma (IFN-gamma) in reproduction, we have examined its effects on cytokine production by human endometrial stromal cells (ESC). Concentrations of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1), and macrophage colony-stimulating factor (M-CSF) in the culture media of normal ESC and an endometrial stromal sarcoma cell line, MaMi, were measured using an enzyme-linked immunosorbent assay. Both non-stimulated ESC and non-stimulated MaMi cells constitutively secrete IL-6, IL-8, MCP-1, and M-CSF. In a dose-dependent manner, IFN-gamma increased the concentrations of IL-6, MCP-1, and M-CSF and reduced the concentrations of IL-8 in ESC and MaMi cells. These results suggest that IFN-gamma produced by both decidual inflammatory cells and the developing embryo plays a role in the maintenance of early pregnancy by modulating the production of these cytokines by human ESC.

Cells, Cultured

Magnetic resonance imaging of fetal autosomal recessive polycystic kidney disease.

We present a case of fetal autosomal recessive polycystic kidney disease (ARPKD) at 34 weeks of gestation, diagnosed by magnetic resonance imaging (MRI). MRI demonstrated enlarged fetal kidneys that were low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. These MRI findings suggested a high water content in the renal parenchyma, consistent with the innumerable, tiny renal cysts present in ARPKD.

Adult

A case of primary non-Hodgkin's lymphoma of the uterine cervix treated by combination chemotherapy (THP-COP).

We present a case of primary non-Hodgkin's lymphoma of the uterine cervix, Ann Arbor stage IE. This 64-year-old multiparous Japanese woman showed markedly elevated serum levels of lactate dehydrogenase (LDH) and of soluble interleukin-2 receptor (sIL-2R) at the time of diagnosis. Combination chemotherapy was administered and consisted of pirarubicin, cyclophosphamide, vincristine sulfate, and prednisolone (THP-COP). After 3 courses of such therapy, the serum levels of LDH and of sIL-2R decreased within normal limits, and the patient achieved a complete remission.

Antineoplastic Combined Chemotherapy Protocols

Increased serum concentrations of soluble vascular cell adhesion molecule-1 in uterine cervical cancer.

The purpose of this investigation was to determine the serum concentration of soluble vascular cell adhesion molecule-1 (sVCAM-1) in women with squamous cell carcinoma of the cervix. Serum samples were obtained from 38 Japanese women with squamous cell carcinoma of the cervix before initial treatment (12 in stage 0, 7 in stage I, 5 in stage II, 9 in stage III and 5 in stage IV), 7 patients with a recurrence of this cancer, and 18 healthy female volunteers. Serum sVCAM-1 was measured with a sandwich enzyme-linked immunosorbent assay. Serum concentrations (means+/-SD) of sVCAM-1 in the healthy volunteers, the patients with cervical cancer in stages 0-IV and in the patients with recurrent tumors were 597.2+/-151.4, 690.1+/-214.2, 1,234.8+/-466.1, 1,159.8+/-825.8, 1,529.6+/-662.0, 1,053.0+/-228.8, and 1,134.8+/-211.3 ng/ml, respectively. Values for patients with stages I-IV or recurrent cervical cancer were significantly increased compared to those for healthy volunteers (p < 0.05). Results suggest that sVCAM-1 is shed from endothelial cells in the cancerous tissue.

Carcinoma, Squamous Cell

CT and MRI findings in a case of pelvic schwannoma.

We compared the diagnostic utility of computed tomography (CT) and magnetic resonance imaging (MRI) in a patient with a pelvic schwannoma. This 46-year-old woman was admitted for evaluation of a retroperitoneal pelvic mass and myoma uteri. The retroperitoneal pelvic mass had been detected by a CT scan at a routine health examination. A CT scan revealed a well-circumscribed cystic tumor (4 x 3 cm) at the right internal obturator muscle portion. The CT number of the inner part of the tumor was 21. Only the cyst wall was enhanced by injection of a contrast medium. MRI showed a 4 x 3 x 3-cm retroperitoneal cystic tumor that demonstrated low-intensity signals on T1-weighted images and high-intensity signals on T2-weighted images. Small areas of low intensity inside the tumor were observed on T2-weighted images. Histological examination revealed a typical schwannoma of mixed Antoni type A and type B. These findings indicate that both MRI and CT are useful for diagnosis of retroperitoneal schwannomas.

Female

MaMi, a human endometrial stromal sarcoma cell line that constitutively produces interleukin-6, interleukin-8, and monocyte chemoattractant protein-1.

BACKGROUND: Uterine endometrial stromal sarcoma is a rare neoplasm with a morphology that closely resembles that of the proliferative endometrial stroma. To understand its pathologic characteristics, we established a novel cell line, MaMi, from a primary culture of an endometrial stromal sarcoma obtained from a 65-year-old Japanese woman. METHODS: We observed the morphology of MaMi cells and performed immunohistochemical analysis on the primary tumor and transplants in nude mice. Prolactin, insulin-like growth factor-binding protein-1, interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, E-selectin, vascular cell adhesion molecule-1, and fibronectin production in the culture medium of MaMi cells were also examined. RESULTS: MaMi cells were shown to exhibit a fibroblast-like morphology in vitro, and they adopted a more elongated appearance in response to 12-O-tetradecanoyl phorbol-13-acetate (TPA). On injection into nude mice, the cells gave rise to subcutaneous tumors. Immunohistologically, both the primary tumor and MaMi cell-induced tumors stained positively with antibodies to neuron-specific enolase or vimentin. MaMi cells constitutively produced IL-6, IL-8, and monocyte chemoattractant protein-1 in vitro. Interleukin-1beta, (100 pmol/L), tumor necrosis factor-alpha (1 nmol/L), and lipopolysaccharide (1 microg/mL) each increased the release of IL-6, IL-8, and monocyte chemoattractant protein-1 by MaMi cells. TPA (10 nmol/L) also stimulated the production of IL-6 and IL-8 by these cells, but inhibited that of monocyte chemoattractant protein-1. CONCLUSIONS: We demonstrated that MaMi cells closely resemble proliferative endometrial stromal cells not only morphologically, but also functionally. This cell line may prove valuable in understanding the role of cytokines produced by tumor cells in the pathogenesis of endometrial stromal sarcoma and may also be useful as an in vitro model of functioning endometrial stromal cells.

Aged

Serum levels of soluble intercellular adhesion molecule-1 (ICAM-1) and the expression of ICAM-1 mRNA in uterine cervical cancer.

The purpose of this investigation was to evaluate the serum level of soluble intercellular adhesion molecule-1 (sICAM-1) in patients with squamous cell carcinoma of the cervix. Serum levels of sICAM-1 were measured by enzyme-linked immunosorbent assay in patients with cervical cancer (stage 0 through IV). Expression of mRNA in tumor tissues was evaluated by reverse transcriptase-polymerase chain reaction. Serum level of sICAM-1 in patients with advanced-stage (II-IV) or recurrent cervical cancer was found to be increased significantly. Expression of ICAM-1 mRNA was observed in most tumor tissues. Results suggest that sICAM-1 is shed from the cancerous tissue in patients with squamous cell carcinoma of the cervix.

Carcinoma, Squamous Cell

Parathyroid hormone-related protein levels in maternal and cord blood.

OBJECTIVE: Our purpose was to determine the plasma levels of parathyroid hormone-related protein in normal pregnant women in each trimester, at 1 month post partum in women using different feeding methods, and in umbilical venous blood. STUDY DESIGN: We studied 40 healthy nonpregnant women, 90 healthy pregnant women (30 in the each trimester), and 140 postpartum women (breast-feeding 74, mixed feeding 33, bottle feeding 33). We also measured the parathyroid hormone-related protein level in umbilical venous blood in 24 women. RESULTS: The means and SDs of the plasma parathyroid hormone-related protein level were 1.04 +/- 0.11 pmol/L (0.81 to 1.26 pmol/L) in nonpregnant women, 1.06 +/- 0.19 pmol/L (0.69 to 1.48 pmol/L) in pregnant women in the first trimester, 1.10 +/- 0.19 pmol/L (0.80 to 1.50 pmol/L) in pregnant women in the second trimester, and 1.17 +/- 0.16 pmol/L (0.86 to 1.57 pmol/L) in pregnant women in the third trimester. At postpartum month 1 the plasma level of parathyroid hormone-related protein was 1.25 +/- 0.23 pmol/L (0.83 to 2.01 pmol/L) in breast-feeding women, 1.17 +/- 0.16 pmol/L (0.84 to 1.53 pmol/L) in mixed-feeding women, and 1.03 +/- 0.16 pmol/L (0.74 to 1.43 pmol/L) in bottle-feeding women. The umbilical venous blood level of parathyroid hormone-related protein was 1.33 +/- 0.32 pmol/L (0.84 to 2.11 pmol/L). The mean plasma level of parathyroid hormone-related protein increased throughout pregnancy and was significantly high in the third trimester and closely associated with the degree of breast-feeding at 1 month post partum. The parathyroid hormone-related protein level in umbilical venous blood was significantly higher than those in any groups of pregnant women. CONCLUSIONS: Parathyroid hormone-related protein produced in the fetoplacental unit, the breast, or both can reach the maternal circulation.

Adult

Vaginal fluid hCG levels for detecting premature rupture of membranes.

OBJECTIVE: To determine if the measurement of hCG levels in vaginal fluid is useful for the diagnosis of premature rupture of membranes (PROM). METHODS: After irrigating the posterior vaginal fornix with 3 mL of sterile saline and procuring vaginal washings, we measured hCG levels. Samples were analyzed from 188 normal pregnant women, 42, 61, and 85 during the first, second, and third trimesters, respectively. Levels of hCG were compared with those of 24 women with confirmed PROM. RESULTS: The median and 95% confidence intervals (CIs) of vaginal fluid hCG levels of normal pregnant women were 37.9 (1.9, 725.6), 9.5 (0.8, 95.8), and 6.3 (0.6, 62.2) mIU/mL during the first, second, and third trimesters, respectively. That of women with PROM was 420.6 (216.3, 918.3) mIU/mL. For the second trimester, sensitivity was 100%, specificity 91.8%, positive predictive value 82.8%, negative predictive value 100%, and accuracy 94.1%; and for the third trimester, sensitivity was 100%, specificity 96.5%, positive predictive value 88.9%, negative predictive value 100%, and accuracy 97.2%, using a threshold value of 50 mIU/mL. CONCLUSION: The hCG level in vaginal fluid is a useful marker of PROM during the second and third trimesters.

Adult