Koyo Yoshida

Aldo-keto reductase family 1, member B10 in uterine carcinomas: a potential risk factor of recurrence after surgical therapy in cervical cancer.

Aldo-keto reductase family 1, member B10 (AKR1B10), an enzyme that converts retinals into retinols is known to detect in non–small cell lung carcinoma (squamous cell- and adeno-carcinomas), but is barely expressed in normal tissues. Since these types of carcinoma occur frequently in the uterus (like in the lung), AKR1B10 may also be overexpressed in two major types of uterine cancer, cervical cancer (CC), and endometrial cancer (EMC). The objective of this study is to investigate AKR1B10 expression in uterine cancer and to analyze its clinical significance. In samples from uterine cancer patients, AKR1B10 was detected in 6 out of 30 (20.0%) CC cases and 6 out of 38 (15.8%) EMC cases. Statistical analysis indicated that AKR1B10 expression was associated with tumor recurrence after surgery and keratinization of squamous cell carcinoma only in CC. Although retinol (a metabolic product by AKR1B10) was observed in the normal epithelium, the molecule was not observed in cancer cells of AKR1B10-positive CC samples suggesting that the recurrence in CC may not depend on the convert of retinals into retinols via AKR1B10, a potential indicator in the management of patients with CC

Sodium butyrate induces growth arrest and senescence‐like phenotypes in gynecologic cancer cells

We demonstrated here the growth‐suppressing effects of sodium butyrate (NaB) on human endometrial and ovarian cancer cells. The arrest of cells at the G1 checkpoint accounted for this effect. NaB‐mediated p21 might arrest endometrial and ovarian cancer cells at the G0/G1 phase by eliciting pRb unphosphorylation. To demonstrate the role of pRb regulation by p21, we measured the sensitivity to NaB of cervical cancer cells in which pRb had been inactivated by HPV E7. The cervical cancer cells displayed a sensitivity in NaB‐mediated G2/M arrest in addition to their sensitivity in G0/G1 arrest. Arrest at G0/G1 and G2/M accompanied induction of senescence‐like phenotypes (SLPs). Most importantly, the effect of NaB on senescence induction was not coupled with the predominance of hypophosphorylated pRb forms in the cervical cancer cells. This suggested that NaB had the potential to elicit SLPs through p21‐mediated withdrawal from cell cycle progression. The consequences of p21 induction were manifold. The effects of NaB on gynecologic cancer cell growth indicated its potential use in cancer treatment. NaB was effective even in the cancer cells with mutant p53 and/or Rb genes by eliciting cell senescence.

New Method to Prevent Bladder Dysfunction after Radical Hysterectomy for Uterine Cervical Cancer

Objective: The purpose was to improve the surgical procedures to prevent bladder dysfunction after radical hysterectomy.

Placental pathology in systemic lupus erythematosus with antiphospholipid antibodies

Systemic lupus erythematosus (SLE) is associated with a poor pregnancy outcome. Antiphospholipid antibodies (APL), which include lupus anticoagulant (LAC) and anticardiolipin antibodies (aCL), are frequently found in patients with SLE, and their presence has been associated with fetal loss. To examine placental pathologic features of SLE patients with APL, we performed a pathologic study on 47 placental tissue samples from 47 pregnant SLE patients with APL (15 patients; four LAC single‐positive patients, seven aCL single‐positive patients, four LAC and aCL double‐positive patients) and without APL (32 LAC and aCL double‐negative patients). The incidence of extensive infarction, decidual vasculopathy, decidual thrombosis and perivillous fibrinoid change, which have been thought to be characteristic lesions of APL placenta, was significantly higher in the LAC and aCL double‐positive patients than in the patients without APL. Conversely, the above‐mentioned lesions between the LAC or aCL single‐positive patients and the APL negative patients did not differ significantly. Among the 15 patients with APL, two of the three patients with both decidual vasculopathy and thrombosis had extensive infarction associated with fetal death. Moreover, the patients having fetal death showed LAC and aCL double‐positivity. In conclusion, this study indicated that the LAC and aCL double‐positivity is an important factor for extensive infarction resulting from decidual vasculopathy and decidual thrombosis in the SLE placenta. Moreover, it was indicated that LAC and aCL double‐positivity is an important risk factor for fetal death in the SLE patient.

Immunoadsorption plasmapheresis as a treatment for pregnancy complicated by systemic lupus erythematosus with positive antiphospholipid antibodies.

PROBLEM: Our purpose was to study the effect of maternal immunoadsorption plasmapheresis (IA) on the outcome of pregnancies complicated by systemic lupus erythematosus (SLE) with positive antiphospholipid antibodies, which were known to have a strong correlation with abortion or stillbirth.

Quantitative peptidomic analysis by a newly developed one‐step direct transfer technology without depletion of major blood proteins: Its potential utility for monitoring of pathophysiological status in pregnancy‐induced hypertension

We have recently developed a new target plate (BLOTCHIP®) for MALDI‐MS. An advantage of this procedure is that it does not require the lowering of protein concentrations in test samples prior to analysis. Accordingly, this new technology enables the detection of peptides present in blood samples, including those that would otherwise be adsorbed to abundant blood proteins and would thus escape detection. Using this technology, we analyzed the peripheral blood of patients with pregnancy‐induced hypertension (PIH; the most common serious complication of pregnancy) to test a potential utility of the technology for monitoring of the pathophysiological status. In the present study, we found 23 characteristic peptides for PIH in the blood serum of pregnant women. Offline LC‐MALDI MS/MS identified 7 of the 23 peptides as fragments derived from kininogen‐1 (three peptides), fibrinogen‐α, complement component C4‐A/B, α‐2‐HS‐glycoprotein and inter‐α‐trypsin inhibitor heavy chain H4. 2‐D scatter plots with combinations of the peptides found in the present study can be grouped for pregnant women with/without PIH, which would be satisfactory reflected for their status. Additionally, the levels of most of these peptides found were significantly decreased by albumin/IgG depletion prior to BLOTCHIP® analysis in accordance with conventional proteomics procedures. These results indicated that BLOTCHIP® analysis can be applied for discovery study of PIH biomarker candidates.

Multiple pregnancy, short cervix, part-time worker, steroid use, low educational level and male fetus are risk factors for preterm birth in Japan: a multicenter, prospective study.

To examine the relationship between preterm birth and socioeconomic factors, past history, cervical length, cervical interleukin‐8, bacterial vaginosis, underlying diseases, use of medication, employment status, sex of the fetus and multiple pregnancy.

Rapid Detection of Chromosome Aneuploidies by Prenatal Interphase FISH (Fluorescence in situ Hybridization) and Its Clinical Utility in Japan

Objective: The purpose of this study was to assess the accuracy, informative rate, detection rate, and clinical utility of prenatal interphase fluorescence in situ hybridization (FISH) analysis of amniotic fluid samples from Japanese women.

Usefulness of Magnetic Resonance Imaging for Accurate Diagnosis of Pfeiffer Syndrome Type II in utero

Objective: To present the usefulness of fetal magnetic resonance (MR) imaging for accurate diagnosis of Pfeiffer syndrome type II. Case and Methods: A 19-year-old woman was referred to us at 29 weeks of gestation for prenatal management of hydrocephalus. Ultrasonography of the fetus showed cloverleaf skull with dilated lateral ventricles, exophthalmos, macroglossia, and a single ventricle of the heart in addition to polyhydramnios. MR imaging was performed at 30 weeks of gestation and revealed cloverleaf skull, dilated lateral ventricles, and broad thumb. Fetal karyotyping indicated 46,XY, but DNA sequence analysis showed a single sequence variation (Nt 1198A>G) in the fibroblast growth factor receptor (FGFR) 2 gene (exon 10). On the basis of these findings, the baby was diagnosed in utero with Pfeiffer syndrome type II. Following counseling, the pregnancy was terminated because polyhydramnios made the patient’s symptoms more severe. The patient delivered her baby vaginally at 34 weeks of gestation. The baby’s birth weight was 2,298 g; the baby was declared dead at 25 min after birth. Conclusion: The detailed findings obtained by a combination of ultrasound that included three-dimensional and MR imaging and confirmation sought via molecular testing led to an accurate diagnosis of Pfeiffer syndrome type II in utero.

Huge seminoma developed in a patient with testicular feminization

We report a 36‐year‐old patient who presented with primary amenorrhea and was found to have a giant abdominal tumor. There was a family history of primary amenorrhea in her two aunts. Physical and hormonal examinations as well as chromosomal analysis led to a diagnosis of testicular feminization. The patient underwent tumorectomy along with pelvic and para‐aortic lymphadectomy. The pathological diagnosis was bilateral seminoma of the testis with metastasis to para‐aortic lymph nodes. Nowadays, cases of undiagnosed seminoma developing into a huge abdominal mass in patients with testicular feminization are rarely encountered, since surgical castration is generally recommended as early as possible after puberty. In testicular feminization, the risk of malignant transformation of the dysgenetic male gonads increases substantially after puberty. Early and correct diagnosis together with careful follow‐up are critically important in managing testicular feminization, a rare congenital disorder.