Kazunori Hoshimoto

Characterization of five marker levels of the hemostatic system and endothelial status in normotensive pregnancy and pre-eclampsia

Abstract:  Objectives : Pre‐eclampsia is associated with changes in the hemostatic system and endothelial status. Urinary 11‐dehydrothromboxane B 2 /creatinine (11‐DTXB 2 /Cr) is a marker for platelet activation and vascular constriction, thrombin–antithrombin complex (TAT) for thrombin formation, serum thrombomodulin (TM) for endothelial damage, and β‐thromboglobulin (β‐TG) and platelet factor 4 (PF‐4) for platelet activation and releasing reaction. The present study attempted to evaluate these five markers in normotensive pregnancy and pre‐eclampsia. Methods: These five markers were simultaneously measured in urine and blood samples from 25 women who were not pregnant (group 1, controls), 31 women with normotensive pregnancy (group 2, second controls), 22 women with mild pre‐eclampsia (group 3), and 21 women with severe pre‐eclampsia (group 4). The average gestational age was 36 wk. Results: The 11‐DTXB2/Cr, TAT, and β‐TG levels were significantly higher (P < 0.01) in groups 2, 3, and 4 than in group 1. The TM and β‐TG levels were significantly higher (P < 0.05) in group 3 than in group 2. The TM, β‐TG, and PF‐4 levels were increased significantly (P < 0.05–0.01) in group 4 compared to those in groups 1, 2, and 3. Conclusions: Platelet aggregation, vascular constriction, and thrombin formation (detected by 11‐DTXB2/Cr and TAT) may be markedly enhanced even in group 2, but further enhancement may be relatively slight in groups 3 and 4. In contrast, endothelial damage (determined by TM) and platelet release of PF‐4 may not increase significantly in group 2, but they may increase in group 4. Platelet‐release of β‐TG may be enhanced in groups 2, 3, and 4. Endothelial damage and platelet‐releasing reaction (detected by PF‐4 and β‐TG) may be significantly more enhanced in group 4 than in group 3.

Increased Levels of Macrophage Colony‐Stimulating Factor in the Placenta and Blood in Preeclampsia

PROBLEM: Macrophage colony‐stimulating factor (M‐CSF) is considered an essential cytokine for placental growth and maintenance. We evaluated whether M‐CSF levels in the placenta and blood in preeclampsia differed from those in normal pregnancies.

Changes in Plasma Soluble CD26 and CD30 during Pregnancy: Markers of Th1/Th2 Balance?

The theory that the Th1 and Th2 cell ratio shifts towards Th2 dominance during pregnancy may improve fetal survival has gained support from recent studies. Also, the variation in the Th1/Th2 cell ratio is reportedly associated with intrauterine growth retardation and preeclampsia. On the basis of these findings, the analysis of the Th1/Th2 balance may be useful in predicting severe complications during pregnancy. However, simple methods for the analysis of Th1/Th2 balance are presently not available. Recently, it has been reported that regulation of CD26 cell surface expression correlates with the production of Th1-like cytokines. On the other hand, previous studies proposed that the sCD30 molecule is an activation marker useful for evaluation of a Th2 immune response. It is, therefore, possible that the analysis of the Th1/Th2 balance during pregnancy by measuring plasma sCD26 and sCD30 simultaneously is a simple and useful method. We herein demonstrate that combined analysis of sCD26 and sCD30 is a potent surrogate tool to evaluate the Th1/Th2 balance during pregnancy.

The levels of five markers of hemostasis and endothelial status at different stages of normotensive pregnancy

Background.  Urinary 11‐dehydrothromboxane B2/creatinine (11‐DTXB2/Cr) is a marker for in vivo platelet activation and vascular constriction, blood thrombomodulin (TM) for endothelial damage and associated thrombosis, thrombin–antithrombin complex (TAT) for thrombin formation, and β‐thromboglobulin (β‐TG) and platelet factor 4 (PF‐4) for in vivo platelet activation and releasing reaction. Little is known about the quantitative relationship among them during pregnancy. The present study investigated levels of five markers at different stages of normotensive pregnancy.

Plasma Levels of Soluble Fas during Normal Pregnancy

The Fas/Fas ligand system could reportedly help to identify a mechanism for maternal immunotolerance of the fetus in human pregnancy. However, there are few reports on soluble Fas (sFas) which is an inhibitor of apoptosis during normal pregnancy. Therefore, ascertaining plasma sFas levels during pregnancy would be of interest. The subjects studied were 10 nonpregnant healthy women and 20 healthy pregnant women in the first and third trimester with singleton gestations. The plasma sFas was measured by sandwich enzyme-linked immunosorbent assay. The mean concentration of sFas was significantly decreased in normal pregnant women in the first trimester compared to age-matched control subjects, and it did not differ significantly between normal pregnant women in the third trimester and age-matched control subjects. From these results, we presume that the decreased plasma sFas plays an important role in maternal immunotolerance in the first trimester of pregnancy.

Mature adrenomedullin concentrations in plasma during pregnancy

Objective: Adrenomedullin is a novel peptide that exerts a potent, dose-dependent and long-lasting hypotensive effect. In human plasma, adrenomedullin consists of two molecular forms: mature and immature. Immature adrenomedullin is much less bioactive than mature adrenomedullin. Although a gradual increase in plasma adrenomedullin has been reportedly observed as pregnancy progressed, mature adrenomedullin has not been examined. The aim of this study was to elucidate the plasma level of mature adrenomedullin in pregnant women. Methods: We measured the concentrations of mature adrenomedullin in ten pregnant women in the first trimester, ten pregnant women in the third trimester, and ten non-pregnant controls with the immunoradiometric assay. Results: The mean concentration of mature adrenomedullin was significantly increased in pregnant women in the first trimester compared to age-matched non-pregnant subjects (p < 0.05). The mean concentration of mature adrenomedullin was significantly increased in pregnant women in the third trimester compared with pregnant women in the first trimester (p < 0.005). Conclusion: Our study demonstrated that concentrations of mature adrenomedullin were elevated in pregnant women compared with non-pregnant women and its concentration in the third trimester was significantly higher than that in the first trimester.

Increased Excretion of N-Acetyl-β-D-Glucosaminidase and β2-Microglobulin in Gestational Week 30

ABSTRACT Background Little is known about when the urinary excretion of a combination of N -acetyl- β - D -glucosaminidase(NAG) and β 2 -microglobulin ( β 2 MG) concentration [relative to creatinine (Cr)] reaches maximal values during uncomplicated normotensive pregnancy. This study was thus designed to analyze when urinary excretion of biochemical parameters was increased during normotensive pregnancy. Methods NAG, β 2 MG, total protein, albumin, and Cr were simultaneously measured in random (untimed) midstream urine samples from 22 healthy non-pregnant women and from 82 normotensive pregnant women (22 in gestational week 20, 25 in week 30, and 35 in week 37). Results NAG/Cr and β 2 MG/Cr ratios were significantly higher ( P β 2 MG/Cr ratios showed maximal values in gestational week 30. The total protein/Cr ratio was significantly higher in gestational weeks 20, 30, and 37 than in the control subjects. The albumin/Cr ratio was significantly higher in women in gestational week 30 and 37 than in women in gestational week 20 and in the control subjects. Conclusions The excretion of both NAG and β 2 MG relative to Cr was increased and showed the maximal values in gestational week 30 during normotensive pregnancy. The increase in a tubular enzyme (NAG) might be caused by renal tubular damage, and that in a low molecular weight protein ( β 2 MG) might result from decreased renal tubular reabsorption. These findings suggest that renal tubular damage and reabsorption dysfunction were increased in gestational week 30.

Primary Small Cell Neuroendocrine Carcinoma of the Vagina

Primary small cell neuroendocrine carcinoma of the vagina is extremely rare and very aggressive. Nineteen patients with this cancer have been reported in the English-language literature to date. We report a 51-year-old woman with this cancer. Punch biopsy specimens of the vaginal tumor were studied. Electron microscopy demonstrated neuroendocrine granules in the cytoplasm. Tumor cells were strongly stained for cytokeratin, neuron-specific enolase, chromogranin A and serotonin. These findings were consistent with small cell neuroendocrine carcinoma. The patient was treated with combination chemotherapy. The cancer mass completely disappeared after five cycles of the therapy. The patient is still alive without metastasis 41 months after diagnosis. This is the first report of such a remarkable effect of combination chemotherapy on small cell neuroendocrine carcinoma of the vagina.

Osteochondroma of the Pubic Symphysis Associated with Sexual Disturbance

Osteochondroma of the pubic symphysis is a rare benign skeletal tumor. We report here a case of an osteochondroma of the pubic symphysis associated with a sexual disturbance, where a computed tomography scan clearly showed a tumor lesion of the pubic symphysis. The case is reported not only because of its rarity but also because it is important that gynecologists should bear this disease in mind, since a patient with this tumor may not visit an orthopedist but a gynecologist.

Macrophage colony-stimulating factor levels in amniotic fluid before and after the onset of labor do not differ in normal pregnancies

Problem:  Macrophage colony‐stimulating factor (M‐CSF) promotes placental growth and maintenance. M‐CSF also regulates trophoblast invasion into the placental bed. We evaluated whether M‐CSF levels in amniotic fluid during labor contributing to subsequent delivery differed from those before the onset of labor in normal pregnancies.