A molecular variant of angiotensinogen associated with preeclampsia.

Pregnancy-induced hypertension (PIH) is a heterogeneous disorder which complicates 5-7% of all pregnancies and remains a leading cause of maternal, fetal and neonatal morbidity and mortality. Severe preeclampsia is the most distinctive and life-threatening form; a multi-system disorder more common in first pregnancies, it is characterized by high blood pressure and proteinuria. In a series of Caucasian women with pregnancy-induced hypertension, we have observed a significant association of preeclampsia with a molecular variant of angiotensinogen, T235, found previously to be associated with essential hypertension. This finding is corroborated in a sample ascertained in Japan. Together, these observations support a new pathophysiological interpretation of preeclampsia and of its relation to some forms of essential hypertension.

Meiotic segregation analysis in male translocation carriers by using fluorescent in situ hybridization.

Balanced reciprocal and Robertsonian translocations are the most common structural chromosome abnormalities in humans, with incidences of 0.7 and 1.23 per 1000. These translocations can affect fertility and/or pregnancy outcome because of possibly impaired production of gametes with an unbalanced zygote caused by the parental arrangement. Fertility problems in male translocation carriers are because of various degrees of sperm alterations that are directly related to the disturbance of the meiotic process. Investigation of human sperm chromosomes was performed by karyotyping spermatozoa after penetration of zona-free hamster oocytes, karyotype analysis now being possible to analyse the segregation patterns by using fluorescent in situ hybridization (FISH). Here, we document the results of meiotic segregation analysis for four Robertsonian and four reciprocal translocation carriers by FISH. In the sperm of Robertsonian translocation males, the majority of spermatozoa were normal/balanced. On the other hand, males with reciprocal translocations demonstrated a high rate of unbalanced spermatozoa of about 50% on meiotic segregation, with an unusually high rate (23.5%) of 3 : 1 segregation. This knowledge can be used for genetic counselling of families with these types of translocations.

Biological behavior of cloned cells of human malignant fibrous histiocytoma in vivo and in vitro.

A human malignant fibrous histiocytoma cell line was established in vitro. Cells showed a wide variety of morphologies, although the karyotype study showed that the tumor was monoclonal in origin because of the presence of unique marker chromosomes in 100% of the cells examined (50 of 50). Cells were cloned according to their characteristic morphologies and biological behavior in culture. The cloned cells were sparse spindle, packed spindle, epithelioid, and lymphoid. In colonies, sparse spindle cells grew separately from each other without cell to cell contact but produced a cartwheel pattern at confluency. Packed spindle cells grew in a tightly packed fashion and produced a storiform pattern at confluency. Epithelioid cells were spindle shaped as individuals but became epithelioid when in contact with each other and produced many multinucleated giant cells at confluency. Lymphoid cells were spindle shaped as individuals but became spherical at confluency. When tumors were grown in nude mice after transplantation of these cloned cells, the histology was shown to be unrelated to morphology in culture and was epithelioid (histiocytic), as was the original tumor. These results show that (a) a single cell derived from malignant fibrous histiocytoma cells exhibits a wide range of phenotypical expression in vitro, (b) cells have their own morphological and biological characteristics in vitro, which (c) however, are easily influenced by environmental factors and (d) which are unstable and even interchangeable. These characteristics may contribute to the endless variety of cellular forms and growth patterns of malignant fibrous histiocytomas in humans.

Tumor hypoglycemia induced in nude mice by a heterotransplantable human ovarian carcinoma line (OCL-1).

Tumor hypoglycemia induced by a heterotransplantable human ovarian carcinoma line (OCL-1) was described. Plasma glucose decreased to 36 +/- 9 mg/dl (S.D.) at 8 to 12 weeks after the transplantation. Significant amounts of immunoreactive insulin and insulin-like active substance could not be detected in tumor tissues. Plasma immunoreactive insulin levels were low, and glucagon levels were high in OCL-1-bearing nude mice, compared with the control. Light- and electron-microscopically, tumor cells possessed large amounts of glycogen, and this finding was also biochemically confirmed. OCL-1 tumor showed high glycogen synthetase activity compared with other control tumors, while glycogen phosphorylase activity was the same level as other tumors. The high glycogen synthetase activity was considered to be the cause of glycogen accumulation in tumor cells. Hypoglycemia in OCL-1-bearing nude mice was considered to be caused by abnormal redistribution of glycogen, i.e., marked accumulation of glycogen in tumor tissues and depletion of glycogen in the host liver. This OCL-1 tumor-nude mice system was thought to be a good model for research on the mechanisms of tumor hypoglycemia occurring in cancer patients with nonpancreatic islet cell tumors.

Progesterone inhibits apolipoprotein-mediated cellular lipid release: a putative mechanism for the decrease of high-density lipoprotein.

In order to investigate the mechanism for female gonadal hormones to regulate the plasma high-density lipoprotein (HDL) level, the effect of 17 beta-estradiol and progestogens was examined in vitro on the assembly of HDL by free apolipoprotein A-I (apoA-I) with cellular cholesterol and phospholipid. ApoA-I generated HDL particles by removing cholesterol and phospholipid from human fibroblasts, MRC-5. While 17 beta-estradiol did not influence this reaction, progesterone suppressed the removal by apoA-I of both cholesterol and phospholipid, with the extent of the inhibition more for cholesterol than phospholipid. Three other synthetic progestogens showed the similar inhibitory effect on the cellular cholesterol release. Cellular cholesterol de novo-synthesized from mevalonolactone entered more into the acyl-esterified cholesterol compartment and less to the unesterified compartment in the presence of progesterone. On the other hand, progesterone did not influence the overall mass ratio of free and esterified cholesterol in the cell. Cell-surface cholesterol was also uninfluenced by progesterone when probed by extracellular cholesterol oxidase reaction or by diffusion-mediated cellular cholesterol release to cyclodextrin. Neither caveolin-1 nor ABCA1 expression was influenced by progesterone. Progesterone thus seems primarily to alter the specific intracellular cholesterol compartment that is related to the apoA-I-mediated HDL assembly. This mechanism might contribute to the decrease of plasma HDL by administration of progestogen in women under hormone replacement therapy.

Prenatal diagnosis of oculocutaneous albinism by analysis of the fetal tyrosinase gene.

Tyrosinase-negative oculocutaneous albinism, the most severe subtype of a heterogeneous group of albinism, is an autosomal recessive trait caused by mutations in the tyrosinase gene. Prenatal diagnosis had been made previously only by evaluating fetal skin obtained by biopsy, an invasive procedure that cannot be performed earlier than 19 weeks of gestation. A pregnant mother of a 9-year-old Japanese boy with tyrosinase-negative oculocutaneous albinism wanted a prenatal diagnosis. Polymerase chain reaction amplification and allele-specific oligonucleotide hybridization revealed that the child is homozygous and the parents heterozygous for the pathologic mutation of the tyrosinase gene in exon 2 (single base insertion) but not for the one in exon 1. Prenatal diagnosis was made by analyzing the tyrosinase gene in fetal cells obtained by amniocentesis at 14 weeks of gestation, which demonstrated that the fetus was heterozygous for mutant tyrosinase gene. Pregnancy was therefore continued and a normal male infant was born. This procedure, the analysis of the fetal genomic tyrosinase DNA, is a rapid and reliable approach to the prenatal diagnosis of oculocutaneous albinism at a relatively early stage of pregnancy and is safer and less invasive than previous methods using fetal skin biopsy.

Novel mutations in the LAMB3 gene shared by two Japanese unrelated families with Herlitz junctional epidermolysis bullosa, and their application for prenatal testing.

The LAMB3 gene encoding the beta3 chain of laminin 5 is a candidate gene for mutations in the autosomal recessive blistering skin disorder, junctional epidermolysis bullosa. In this study, we performed genetic analyses in two unrelated Japanese families with Herlitz junctional epidermolysis bullosa and identified two novel nonsense mutations in the LAMB3 gene. One of them, Q166X (CAG --> TAG), was found in the maternal allele of family 1 and the paternal allele of family 2. Conversely, the other mutation, W610X (TGG --> TGA), was found in the paternal allele of family 1 and the maternal allele of family 2. Thus, probands of both families were compound heterozygotes for these nonsense mutations. Haplotype analyses with intragenic LAMB3 polymorphisms suggested that both mutations had arisen independently in these two families. Both mutations create a premature translation termination codon predicting truncated beta3 chains that lead to absent expression of laminin 5 in the epidermal basement membrane zone. Based on these results, DNA-based prenatal diagnosis was performed by chorionic villus sampling for subsequent pregnancies in both families. Both fetuses were found to be heterozygous carriers of the W610X mutation together with a normal LAMB3 allele, indicating that they were phenotypically unaffected. These findings expand the repertoire of LAMB3 mutations in junctional epidermolysis bullosa, and emphasize the notion that premature termination codons in both alleles of the laminin 5 genes result in Herlitz junctional epidermolysis bullosa.

Gonadotropins and cytokines affect luteal function through control of apoptosis in human luteinized granulosa cells.

The luteal phase in the normal human menstrual cycle is known to be about 14 days. The physiological mechanisms that regulate the corpus luteum remain to be clarified, although apoptosis is reported to be involved. This study was undertaken to investigate the regulation of luteal function by gonadotropins, cytokines, and PGs, concentrating attention on the incidence of apoptosis and its molecular mechanisms in cultured human luteinized granulosa cells collected at oocyte pick-up from patients undergoing in vitro fertilization and embryo transfer. Clusters of granulosa cells were pipetted in 0.1% hyaluronidase in phosphate-buffered saline. After cell separation by centrifugation using Ficoll-Paque, 1 x 104 viable cells/mL in RPMI 1640 medium with 10% FCS were used for experimentation. Substances added were FSH (100 ng/mL), hCG (100 ng/mL), LH (100 ng/mL), interleukin-1beta (IL-1beta; 10 ng/mL), transforming growth factor-beta1 (TGFbeta1; 10 ng/mL), macrophage colony-stimulating factor (MCSF; 10 ng/mL), tumor necrosis factor-alpha (TNFalpha; 10 ng/mL), and PGF2alpha (10 ng/mL). After 24-h culture at 37 C under 5% CO2 and air, cells were fixed with 4% neutral buffered formalin and stained with Hoechst 33258. Apoptotic bodies were counted under a fluorescence microscope, and immunostaining was performed using anti-Fas, Fas ligand, Bcl-2, Bax, and p53 antibodies. Incidences of apoptotic bodies in the group without substance addition were 0.7 +/- 0.2% (0 h), 5.9 +/-0.6% (24 h), and 7.9 +/- 1.2% (48 h); spontaneous increase was significant at the latter time points. Defining the incidence at 24 h as 100%, values after treatment were: FSH, 57%; LH, 84%; hCG, 44%; IL-1beta, 76%; TGFbeta1, 52%; M-CSF, 50%; TNFalpha, 177%; and PGF2alpha, 147%. Significant suppression was observed with FSH, hCG, TGFbeta1, and M-CSF (P < 0.01). On the other hand, significant induction occurred with TNFalpha and PGF2alpha (P < 0.01). On immunostaining, the incidence of stained cells with anti-Fas, Fas ligand, Bax, and p53 antibody was increased after 24-h incubation without addition. This was reduced by hCG, TGFbeta1, and M-CSF. No stained cells were observed with anti-Bcl-2 antibody before or after incubation. In conclusion, our results suggest that both gonadotropins (FSH and hCG) and cytokines (TGFbeta1 and M-CSF) may be involved in the support of luteal function via suppression of apoptosis, and that TNFalpha and PGF2alpha may contribute to ovarian dysfunction and/or luteal regression via its induction in human luteinized granulosa cells. Our results also suggest that Fas, Fas ligand, p53, and Bax may play roles in this apoptosis controlled by hCG, TGFbeta1, and M-CSF.

Characterization of changes in mechanical responses to histamine in omental resistance arteries in pre-eclampsia.

Changes in the effect of histamine on the smooth muscle of resistance arteries in pre-eclampsia were investigated by measuring isometric contractions in endothelium-denuded strips of omental resistance arteries from pre-eclamptic and normotensive pregnant women (pregnancy-term matched). Histamine (0.03 -1 microM) caused concentration-dependent relaxation of the contraction induced by 9, 11-epithio-11,12-methano-thromboxane A(2) (STA(2)) in strips from both groups. Sensitivity (for pre-eclampsia: pD(2)=6.66+/-0.04, n=5 and for normotensive pregnant women: pD(2)=7.07+/-0.03, n=10, P<0.001) was lower and the maximum response (90.6+/-0.6% vs 95.5+/-1.1%, P<0.05) was smaller in strips from pre-eclamptic women. Although 8-bromoadenosine-3', 5'-cyclic monophosphorothioate (Sp-isomer: Sp-8-Br-cAMPS, 0.1 - 0.3 mM), a phosphodiesterase (PDE)-resistant activator of adenosine-3',5'-cyclic monophosphate (cyclic AMP)-dependent protein kinase, concentration-dependently attenuated the contraction induced by STA(2) in strips from both groups, the sensitivity (for pre-eclampsia: pD(2)=3.68+/-0.04, n=5 and for normotensive pregnant women: 3.94+/-0.09, n=7, P:=0.02) was lower and the maximum response (64.2+/-2.4% vs 74.9+/-4.4%, P:<0.05) was smaller in pre-eclampsia. In beta-escin-skinned strips, the pD(2) value for the contraction-inducing effect of Ca(2+) did not differ significantly between the two groups (for pre-eclampsia, n=6; for normotensive pregnant women, n=6). Thus, omental resistance arteries from human subjects with pre-eclampsia showed (i) a weaker H(2)-receptor-mediated relaxation to histamine and (ii) a weaker cyclic AMP-analogue-induced relaxation, suggesting that the reduced action of histamine may be partly due to a decreased effect of cyclic AMP.

Developmental analysis of cardiovascular system of 45,X fetuses with cystic hygroma.

There have been few pathological investigations of 45,X embryos and fetuses from a developmental point of view. Since most 45,X embryos and fetuses are lost prenatally, it is important to investigate them morphologically in order to elucidate the pathogenesis of the abnormalities. In this study, 13 45,X fetuses with cervical cystic hygroma were examined between 12 and 23 weeks of pregnancy. Every case had a hypoplastic thymus. The aortic valve was bicuspid in 11 cases and unicuspid in 2 cases. The aortic arch showed tubular hypoplasia between the left carotid artery and the left subclavian artery in 12 cases and type B interruption in one case. Smooth muscle cells and elastic fibers were reduced in number in the hypoplastic aortic arch. These results suggest hypoplastic development of the fourth branchial arch. Combined abnormalities between the aortic arch and aortic valve are not infrequently observed in DiGeorge anomaly. A similar developmental mechanism apparently underlies the pathogenesis of 45,X embryos. Possible genes causing the abnormalities are discussed.

Significance of cardiovascular malformations in cystic hygroma: a new interpretation of the pathogenesis.

Fetuses with cystic hygroma or loose skin of the neck were studied chromosomally and phenotypically to clarify the relation between neck abnormality and cardiovascular malformations. Of 12 fetuses, 9 had chromosome abnormalities: 4 with 45,X, 3 with trisomy 21, one each with trisomy 13, dup 6q. One had normal chromosomes. Two cases, in which chromosome analysis was unsuccessful, were morphologically suspected to be trisomy 13. Nine of the 12 fetuses had either bilateral cystic hygroma of the neck (7 cases) or nuchal bleb (2 cases: trisomy 13 and dup 6q). Two of the 3 remaining cases (trisomy 21) had loose skin of the neck, and one had edematous swelling of the skin of the neck. Except for the last case of trisomy 21, 11 fetuses (91.7%) had severe and/or rare cardiovascular malformations. They were divided into 3 major groups: a) spectrum of hypoplastic left heart syndrome (45,X and dup 6q), b) double outlet right ventricle, agenesis of semilunar valve (trisomy 13), and c) abnormality of atrioventricular orifice or valves (trisomy 21). One fetus with normal chromosomes had persistent left superior vena cava instead of absent right one and calcification of myocardium. Histological observation of edematous skin demonstrated the abnormal distribution of lymph vessels, including their absence. Some cases showed hypoplastic thymus. To integrate the findings of the present study and the descriptions in the literature, a pathogenesis is hypothesized in relation to migration of neural crest cells and extracellular matrix.

Prenatal diagnosis as a test for genodermatoses: its past, present and future.

The prenatal diagnosis (PND) of severe hereditary skin diseases started in the early 1980s using fetal skin biopsy techniques based on ultrastructural and immunohistochemical abnormalities of the fetal skin. Recent success in identifying responsible genes and demonstrating mutations in such genes has set the stage for DNA-based PND in the 1990s. Common examples of skin conditions which can be prenatally diagnosed include epidermolysis bullosa, oculocutaneous albinism and Harlequin ichthyosis in which the severity of the clinical phenotype appears to justify PND in families at risk. More recently, preimplantation diagnoses of inherited diseases have become possible using in vitro fertilization techniques. The diagnosis consists of a blastomere biopsy of the six to ten-cell embryo and a DNA analysis of single blastomeres. Disease-free embryos are selected for transfer to the uterus, thereby avoiding the need for termination of a fetus found to be affected by conventional PND. Furthermore, carrying out a PND using a single fetal cell from the maternal blood, such as nucleated erythrocytes, has become technically feasible. Although there are many questions that remain unanswered, the outlook for further development of noninvasive PND in the future appears optimistic.

Histology of fetal eyes with oculocutaneous albinism.

The diagnosis of tyrosinase-negative oculocutaneous albinism (OCA) was made in a 19-week-old fetus by skin biopsy. Because the parents had an 11-year-old son with tyrosinase-negative OCA, they requested that the fetus be aborted at the 20th week of gestation. A histological analysis of the eyes was performed. Throughout the retina, the ganglion cell layer was separated from the inner neuroblastic layer by the inner plexiform layer. However, the number of ganglion cells was decreased and the nerve fiber layer was immature. Bipolar and horizontal cells had begun to segregate into the inner nuclear layer. Rods and cones were identifiable in the posterior, but not peripheral, retina. Cones were more numerous in the center of the retina, and no rod-free area was identifiable. In addition, the ciliary body (epithelial folds, blood vessels in the mesodermal connective tissue core, and ciliary muscle) was less developed than in a normal fetus. Melanosomes in the retinal pigment epithelium only contained filaments without melanization and were therefore classified as stage I or II melanosomes. However, the ciliary epithelium also contained some stage III melanosomes with melanin adherent to the filaments.

Secretory leukocyte protease inhibitor in ovarian endometriomas following GnRH agonist therapy.

OBJECTIVE: To determine whether expression of secretory leukocyte protease inhibitor is affected in tissue and peritoneal fluid of women with ovarian endometriomas treated with GnRH analogues. METHODS: In 32 women with endometriomas (17 untreated and 15 treated with GnRH analogue) and 21 with ovarian cystadenomas, we examined the expression of secretory leukocyte protease inhibitor messenger RNA (mRNA) by Northern blot analysis; protein distribution was measured immunohistochemically. Concentrations of secretory leukocyte protease inhibitor in peritoneal fluid were measured by enzyme-linked immunosorbent assay. Expression of secretory leukocyte protease inhibitor in endometrioma explants in vitro was also studied with and without the GnRH analogue treatment. RESULTS: Secretory leukocyte protease inhibitor mRNA expression was identified only in untreated endometriomas. In the GnRH agonist-treated endometriomas, the semiquantitative H-score for secretory leukocyte protease inhibitor immunostaining was significantly lower than that for untreated endometriomas (P <.001). The peritoneal fluid of the GnRH agonist-treated women also contained significantly lower concentrations of secretory leukocyte protease inhibitor (median 76 ng/mL, interquartile range 51-131 ng/mL; P <.001) than untreated women (124 ng/mL, 70-186 ng/mL). Secretory leukocyte protease inhibitor in endometrioma explants in vitro was significantly inhibited by the GnRH analogue (P <.05). CONCLUSION: Expression of secretory leukocyte protease inhibitor in tissue and peritoneal fluid of women with ovarian endometriomas was decreased by GnRH agonist treatment.

Fetal cells in the maternal circulation: detection of Y-sequence by gene amplification.

Detection of a Y-specific sequence in the maternal circulation has clinical importance because it would be useful in determining fetal gender in mothers with severe X-linked disorders. The method described in this paper has the advantage of requiring only small amounts of maternal blood. Numerous attempts have been made to identify XY cells in the blood of mothers bearing male fetuses; however, the results have been controversial. In this study, a member of the DYZ1 family and the XY homologous region of the amelogenin gene were used as targets for polymerase chain reaction detection of the Y chromosome. The subjects in this study were a group of 100 pregnant women at 17-20 weeks' gestation and 30 puerperal women who had given birth 2-5 days previously. All of the former underwent amniocentesis, with venous blood samples drawn before the procedure. Forty-five fetuses were confirmed as male by karyotyping amniocytes, and 30 of these were positive for the Y sequence in the DYZ1 region (sensitivity 66.7%). However, ten of the 55 cases diagnosed as female were also positive, giving a specificity of only 81.8%. Thus, the positive and negative predictive values were each 75%. In the amelogenin gene study, a positive Y signal was not detected in any of the cases examined. This study demonstrates the usefulness of polymerase chain reaction detection of Y-specific sequences in the maternal circulation. However, further investigation is necessary to increase the reliability for clinical application, because the method does produce false-positive results.

Modified histamine-induced NO-mediated relaxation in resistance arteries in pre-eclampsia.

We investigated the characteristic changes in histamine-induced, endothelium-derived nitric oxide (NO)-mediated relaxation in human omental resistance arteries seen in pre-eclampsia. Isometric contraction was provoked by a stable analogue of thromboxane A(2) in endothelium-intact strips from both pre-eclamptic and normotensive pregnant women. Histamine (0.3 nM-10 microM) produced a concentration-dependent relaxation of this contraction in both groups. The magnitude of the relaxation induced by histamine (1 microM) was significantly smaller in pre-eclampsia both in the presence and absence of famotidine (H(2)-receptor blocker). In the presence of famotidine, L-N(G)-nitroarginine significantly attenuated the histamine-induced relaxation in strips from normotensive pregnant women but not in those from pre-eclamptic women. The relaxation induced by human atrial natriuretic peptide (0. 1 nM-1 microM) was also significantly smaller in the pre-eclamptic group. It is concluded that the histamine-induced, endothelium-derived NO-mediated relaxation (mediated via H(1)-receptors) is down-regulated in resistance arteries in pre-eclampsia and we suggest that this is due, at least in part, to an attenuation of the action of cyclic GMP in smooth muscle cells.

Embryonic karyotype of abortuses in relation to the number of previous miscarriages.

OBJECTIVE: To examine the frequency of chromosomal abnormalities in products of conception from patients with recurrent miscarriages in relation to the number of previous miscarriages. DESIGN: Retrospective analysis. SETTING: Nagoya City University Medical Hospital. PATIENT(S): A total of 1,309 women with a history of 2-20 consecutive first-trimester abortions. INTERVENTION(S): Chromosomal analysis performed on products of conception with use of a standard G-banding technique. MAIN OUTCOME MEASURE(S): The frequencies of abnormal and normal embryonic karyotypes for each number of previous abortions were studied. The subsequent pregnancy outcome of patients whose previous miscarriages were karyotyped were studied along with the predictive value of karyotyping of previous miscarriages for subsequent miscarriages. RESULT(S): The miscarriage rate increased with the number of previous spontaneous abortions. The frequency of abnormal embryonic karyotypes significantly decreased and that of normal embryonic karyotypes significantly increased with the number of previous abortions. Among 71 patients whose embryonic karyotypes were normal, 44 aborted subsequently, and 23 of 60 patients whose embryonic karyotypes were abnormal aborted subsequently. Patients with a previous normal embryonic karyotype aborted more frequently than those with an abnormal karyotype. CONCLUSION(S): The frequency of normal embryonic karyotypes significantly increases with the number of previous abortions, and a normal karyotype in a previous pregnancy is a predictor of subsequent miscarriage.

Factor XII but not protein C, protein S, antithrombin III, or factor XIII is a predictor of recurrent miscarriage.

OBJECTIVE: To investigate whether a decrease in the values of protein C (PC), protein S (PS), antithrombin III (ATIII), factor XII (FXII), or factor XIII (FXIII) has predictive value for subsequent miscarriages. DESIGN: Prospective study. SETTING: Nagoya City University Medical School. PATIENT(S): A total of 536 patients with a history of two or more first-trimester miscarriages. INTERVENTION(S): One hundred and twelve patients treated with low-dose aspirin were excluded from the analysis. MAIN OUTCOME MEASURE(S): The subsequent pregnancy outcome of 424 patients was compared for abnormal and normal levels of each parameter. RESULT(S): There were no differences in the subsequent miscarriage rates between abnormal and normal values of PC, PS, ATIII, and FXIII. However, the rate with abnormal FXII is significantly higher than that with normal FXII. CONCLUSION(S): A decrease in FXII (but not in PC, PS, ATIII, or FXIII) predicts subsequent miscarriage in patients with a history of first-trimester recurrent miscarriages.

Expression of secretory leukocyte protease inhibitor in women with endometriosis.

OBJECTIVE: To explore endometriosis-related molecules in patients with use of differential display analysis. DESIGN: Prospective study. SETTING: Nagoya City University Medical School, Nagoya, Japan. PATIENT(S): Women with endometriosis (n = 27) and without endometriosis (n = 21). INTERVENTION(S): Surgery was scheduled in the proliferative or secretory phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Differentially expressed products of endometrioma samples were sequenced at nucleotides. One of the candidate genes, secretory leukocyte protease inhibitor (SLPI) gene, was analyzed with use of in situ hybridization and Northern blot analyses. Distribution of SLPI was determined by immunohistochemistry, and the amount of SLPI in the peritoneal fluid and serum was measured by ELISA. RESULT(S): Distinct expression of SLPI messenger RNA could be detected in the endometrial-type epithelium of extrauterine endometriotic tissues and in the eutopic endometrium of women with endometriosis. SLPI was localized in the endometrial-type epithelium of endometriomas immunohistochemically. The amount of SLPI in the peritoneal fluid was markedly elevated in the endometriosis group (91.6+/-6.6 ng/mL compared with 68.4+/-5.3 ng/mL in the controls). CONCLUSION(S): Secretory leukocyte protease inhibitor may be involved in the pathogenesis of endometriosis.

A case of successful conservative chemotherapy for intramural pregnancy.

OBJECTIVE: To describe a rare case of intramural pregnancy diagnosed with the use of magnetic resonance imaging (MRI) and conservatively managed. DESIGN: Case report. SETTING: Department of obstetrics and gynecology in a university hospital. PATIENT: A 33-year-old healthy patient with a history of a partial mole after 3 years of primary unexplained infertility. INTERVENTION(S): Laparoscopic and transvaginal local injections of methotrexate. MAIN OUTCOME MEASURE(S): Transvaginal ultrasound (US) and MRI findings. RESULT: Treatment was successful, with no complications, and the patient's reproductive potential was preserved. CONCLUSION(S): Early detection of intramural pregnancy with the use of transvaginal US is important, and MRI is a useful, noninvasive imaging modality. Chemotherapy with methotrexate is an effective treatment that allows preservation of reproductive potential.