関谷 隆夫

Methylation of histone tails plays a pivotal role in the regulation of a wide range of biological processes. SET and MYND domain-containing protein (SMYD) is a methyltransferase, five family members of which have been identified in humans. SMYD1, SMYD2, SMYD3, and SMYD4 have been found to play critical roles in carcinogenesis and/or the development of heart and skeletal muscle. However, the physiological functions of SMYD5 remain unknown. To investigate the function of Smyd5 in vivo, zebrafish were utilised as a model system. We first examined smyd5 expression patterns in developing zebrafish embryos. Smyd5 transcripts were abundantly expressed at early developmental stages and then gradually decreased. Smyd5 was expressed in all adult tissues examined. Loss-of-function analysis of Smyd5 was then performed in zebrafish embryos using smyd5 morpholino oligonucleotide (MO). Embryos injected with smyd5-MO showed normal gross morphological development, including of heart and skeletal muscle. However, increased expression of both primitive and definitive hematopoietic markers, including pu.1, mpx, l-plastin, and cmyb, were observed. These phenotypes of smyd5-MO zebrafish embryos were also observed when we introduced mutations in smyd5 gene with the CRISPR/Cas9 system. As the expression of myeloid markers was elevated in smyd5 loss-of-function zebrafish, we propose that Smyd5 plays critical roles in hematopoiesis.

BACKGROUND: In the present study, we report on a couple who underwent prenatal genetic diagnosis for autosomal recessive polycystic kidney disease (ARPKD). CASE PRESENTATION: This healthy couple had previously had a healthy boy but had experienced two consecutive neonatal deaths due to respiratory distress resulting from pulmonary hypoplasia caused by oligohydramnios. The woman consulted our facility after she realized she was pregnant again. We promptly performed a carrier test for the PKHD1 gene by target exome sequencing of samples from the couple. A pathogenic mutation was identified only in the paternal allele (c.9008C>T, p.S3003F). The mutation was confirmed by Sanger sequencing of the DNA from formalin-fixed, paraffin-embedded, kidney tissue of the second neonate patient and was not found in the healthy sibling. We then performed haplotype analyses using microsatellite markers scattered throughout the PKHD1 gene. DNA from the amniocentesis was determined to belong to a carrier, and the couple decided to continue with the pregnancy, obtaining a healthy newborn. Subsequent detailed examination of the exome data suggested higher read depth at exons 45 and 46. Multiplex ligation-dependent probe amplification allowed identification of duplication of these two exons. This case suggests the potential usefulness of target exome sequencing in the prenatal diagnosis of the PKHD1 gene in ARPKD. CONCLUSIONS: This is the first report of intragenic duplication in the PKHD1 gene in ARPKD.

Chemiluminescence (CL) of firefly luciferin (Ln) consisting of red and green emission peaks can be generated by dissolving oxygen (O2) gas in deoxygenated dimethyl sulfoxide containing potassium tert-butoxide (t-BuOK) even without the enzyme luciferase. In this study, the characteristics of CL of Ln are examined by varying the concentrations of both Ln ([Ln]) and t-BuOK ([t-BuOK]). The time courses of the green and the red luminescence signals are also measured using a 32-channel photo sensor module. Interestingly, addition of 18-crown-6 ether (18-crown-6), a good clathrate for K(+), to the reaction solution before exposure to O2 changes the luminescence from green to red when [t-BuOK] = 20 mM and [18-crown-6] = 80 mM. Based on our experimental results, we propose a two-pathway model where K(+) plays an important role in the regulation of Ln CL to explain the two-color luminescence observed from electronically excited oxyluciferin via dioxetanone.

OBJECTIVES: With the maturation of the cervical canal during pregnancy, the cervical gland area (CGA) as observed on transvaginal ultrasonography is gradually obscured. The aim of this study was to elucidate the significance of CGA in the late third trimester as a determinant of the outcome of labor. METHODS: We investigated 123 primiparous women with singleton pregnancies at 36-41 weeks' gestation. The women were divided into two groups: a normal delivery group (93 women), which had vaginal delivery without medical intervention, and an induction of labor group (30 women), which required induction of labor after 41 weeks and 0 day. At outpatient prenatal checkups, the Bishop score (BS) was assessed by pelvic examination, and cervical length (CL) and CGA were evaluated by transvaginal ultrasonography. The relationship between each parameter and induction of labor was retrospectively determined and compared. RESULTS: Time-dependent assessment of each outcome determinant showed that the CGA detection rate was higher and the CL was longer in the induction of labor group from 3 weeks to 1 week before delivery at a significant level (P < 0.05); however, the BS was significantly lower in the induction of labor group only at 1 week before delivery (P < 0.05). When multiple logistic regression analysis of the necessity of induction of labor was conducted using BS, CL, and CGA parameters as explanatory variables at 1 week before delivery, CGA alone was shown to be an independent predictor of induction of labor (OR = 6.1, 95 % CI 2.3-16.2). CONCLUSION: The present study suggests that in the late third trimester, evaluation of CGA with transvaginal ultrasonography is most useful in predicting the necessity of induction of labor to prevent post-term delivery.

Connective tissue growth factor (CTGF) has been reported to play critical roles in the tumorigenesis of several human malignancies. This study was performed to evaluate CTGF protein expression in head and neck squamous cell carcinoma (HNSCC). Surgical specimens from 76 primary HNSCC were obtained with written informed consents and the expression level of CTGF was immunohistochemically evaluated. The cytoplasmic immunoreactivity of CTGF in cancer cells was semiquantitatively classified into low and high expression. Among all 76 cases with or without neoadjuvant therapy, low CTGF showed significantly longer (P = 0.0282) overall survival (OS), but not disease-free survival (DFS) than high CTGF. Although low CTGF in patients with stage I, II and III did not result in any significant difference of the OS and DFS, stage IV HNSCC patients with low CTGF showed significantly longer OS (P = 0.032) and DFS (P = 0.0107) than those with high CTGF. These differences in stage IV cases were also confirmed using multivariate analyses. These results suggest that low CTGF in stage IV HNSCC is an independent prognostic factor, despite with or without neoadjuvant therapy.

Recently, as laparoscopic myomectomy (LM) has become increasingly common, reports of intraoperative or postoperative complications have arisen. We experienced a case of massive hemorrhage resulting from a ruptured uterine arteriovenous fistula after LM.<BR>  A 24-year-old woman, nulligravid, presented with hypermenorrhea. She was diagnosed with an 8-cm intramyometrial leiomyoma of the posterior uterus with endometrial deformation. LM was performed. The myoma was soft, its boundaries were not clear, and there was extensive contact with endometrium. Operative time, blood loss, and enucleate weight were 181 minutes, 1,000 ml, and 298g. On a transvaginal ultrasound 25 days after the operation, a cystic lesion was noted in the area of the myomectomy. Color Doppler ultrasonography showed a fountain of blood streaming from a single artery into the cyst, while the size of the cyst was not changed. However, a massive hemorrhage erupted even as we were conferring with the patient in the medical examination room. She underwent emergency laparotomy on the same day. Pulsatile bleeding from a 1mm diameter artery in the wound of the myomectomy was observed. We examined the cyst in detail after ligating the artery. The wall of cyst was a structured fibrous myomatous capsule of a white color with a perforation of the intrauterine part. Blood infiltration and hematoma were not seen at all in the myometrium of the cyst.<BR>  We have performed LM on 406 patients in our hospital. This case was the first of its kind, so we are reporting it as a warning for consideration in the LM of the future.

PURPOSE: The purpose of this study was to assess the clinical features and characteristics of the blood flow in uterine vascular abnormalities using ultrasound and magnetic resonance imaging (MRI). METHODS: A total of 17 women were diagnosed with uterine vascular abnormalities by ultrasound. The clinical characteristics of the patients and the distribution and waveform of the intrauterine vessels were examined using transvaginal gray-scale and Doppler ultrasonography, spin-echo MRI, and MR angiography. RESULTS: The average age of the 17 subjects was 44.3 years, and 5 were postmenopausal women. The number of pregnancies and deliveries was 2.0 and 1.7, respectively. Of the 17 subjects, 7 had a moderate or severe grade of dysmenorrhea and 7 had a history of vascular disease. In all subjects, vaginal ultrasound demonstrated tubular or numerous tortuous anechoic areas in the uterine wall, and Doppler ultrasound showed that the tubular or numerous dilated tortuous vessels had an atypical wave flow, unlike that of an artery or a vein. The distribution of displayed flow varied, and the waveforms of the Doppler ultrasound displayed three patterns. The averages of the pulse Doppler flow indices showed low impedance in the abnormal uterine vessel and the uterine artery, especially in cases of true arteriovenous malformations. MR angiography demonstrated distinct, tortuous, and coiled vascular channels in the pelvis during and just after the arterial phase. CONCLUSION: Characterization of the clinical features of uterine vascular abnormalities is considered to be valuable for obstetricians and gynecologists.

Pregnancy-associated plasma protein-A and -A2 (PAPP-A and -A2) are proteases that cleave insulin-like growth factor-binding proteins (IGFBPs), resulting in local activation of IGF signaling pathways. Here, we examined PAPP-A and -A2 mRNA and protein levels in placenta and maternal sera from women with pre-eclampsia and compared them with samples from uncomplicated pregnancy. PAPP-A2 but not PAPP-A mRNA and protein were elevated in pre-eclamptic placenta (P < 0.01). PAPP-A2 is normally produced in placental syncytiotrophoblast cells and maternal decidua. PAPP-A2 in syncytiotrophoblast cells was dramatically increased in pre-eclampsia. Maternal serum concentrations of PAPP-A2 but not PAPP-A were also significantly elevated in pre-eclampsia as compared with uncomplicated pregnancy. mRNA levels of IGFBP5, a specific substrate for PAPP-A2 protease activity, were also significantly increased, suggesting a potential role for IGFBP5 in fetal and placental growth suppression during pre-eclampsia. However, IGFBP5 protein levels were not increased in placenta from pre-eclampsia, possibly due to cleavage by up-regulated PAPP-A2. These data might imply that PAPP-A2 may be up-regulated in pre-eclamptic pregnancy to compensate for IGFBP5-mediated suppression of the IGF pathway, although final birthweights are still low in pre-eclamptic pregnancy.

一宮市立市民病院今伊勢分院の老人性認知症治療病棟は、他の病院において対応困難であった認知症患者を積極的に受け入れて、身体診療科や一宮市立市民病院本院と連携しながら、その身体合併症診療に力をいれてきた。しかし、平成の市町村大合併に伴う合理化や平成18年度の診療報酬改定などの医療情勢の変化により、大きな影響を受けている。今回筆者らは、自験症例を通じて、現在の老人性認知症患者の身体合併症診療における問題点を明らかにし、診療の実効性を担保するための政策の重要性を強調した。(著者抄録)

We examined clinical and sonographic findings in 112 patients diagnosed as having hemorrhagic ovarian cyst (HOC) who had clinical and transvaginal sonographic follow up. The patients were classified into group A (n=40) with signs and symptoms of acute abdomen and group B (n=72) with no symptoms or mild abdominal pain, and their ultrasonographic and clinical findings were compared. Significant differences were found in mean age, white blood cell (WBC) count, greatest diameter of the mass, shortest diameter of the mass, and size of cross section of the mass. The internal echograms of HOCs were grouped into 4 types: (1) hyperechoic and hypoechoic solid type; (2) reticular or sponge-like type; (3) mixture type of solid and cystic components; and (4) cystic types. In all image types, septum-like or thread-like echoes were seen. Transvaginal sonography (TVS) of type 1, type 2, and type 3 images showed a clear division into hyperechoic and other areas with the passing of time which was finally changed into a cystic pattern and disappeared. HOCs were found more frequently in nulliparous patients (n=79, 70.5%) than in multiparous (n=33, 29.5%). There were many luteal phase (n=86, 76.8%) in comparison with follicular phase (n=13, 11.6%). Thirteen cases were detected during early gestation (n=13, 11.6%). In group A, severe pain reduced or disappeared within 3 h in 37/40 (92.5%) of the patients. Blood flow inside the masses was analyzed in 14 patients by the color Doppler method and showed no significant change. Taken together, this study elucidated the ultrasonographic and clinical characteristics of HOCs, which provide useful information to differentiate HOCs from organic masses and help to avoid unnecessary laparotomy.

Numerous reports have examined the relationship between sonographically determined cervical length and spontaneous preterm birth. Moreover, large screening studies have consistently demonstrated that the shorter the cervical length, the higher the rate of spontaneous preterm delivery. However, the sensitivity and positive predictive value of the cervical length for detecting preterm birth were low. Subsequently, we developed a new sonographic parameter termed "cervical gland area (CGA)". The purpose of this study was to determine whether sonographic cervical findings (shortened cervical length or absence of CGA) at 16 - 19 weeks' gestation could predict spontaneous preterm birth. The absence of CGA as compared to the shortened cervical length showed a higher sensitivity (75.0% vs. 50.0%) and a significantly elevated positive predictive value (54.5% vs. 8.3%) for preterm birth before 32 weeks' gestation. It was concluded that the absence of CGA was a novel and useful sonographic parameter for predicting early spontaneous preterm birth.

Objectives: The aim of this study was to predict massive uterine bleeding during pregnancy and cesarean section in women with placenta previa using transvaginal ultrasonography. Methods: Transvaginal ultrasonography was performed prospectively at and after 28 gestational weeks with follow-up scans at 5- to 7-day intervals until cesarean section in 35 women with placenta previa. The patients were classified into 3 groups based on the following sonographic features of the placental edge in relation to the internal cervical os: type A =two thirds of the placenta from the placental center overlapping the internal os (13 cases) type B =one third of the placenta from the periphery to outside overlapping the internal os (10 cases), and type C =echo-free space (EFS) in the placental edge overlapping the internal os (12 cases). In some cases of type-A placentas, lacunae with blood flow in the placenta from the basal plate to the chorionic plate were also observed. All types were further subdivided based on the presence or absence of associated sponge-like echo (S-echo) in the wall of the uterus adjacent to the placental location. In each type, the relation with the amount of bleeding during hospitalization and preterm delivery was examined. Results: Incidences of sudden massive bleeding during hospitalization were 7.7% (1/13), 10.0% (1/10), and 83.3% (10/12), in types A, B and C, respectively, being significantly higher in type C (p &lt 0.01). The risk of antepartum massive bleeding was also significantly higher in type C (p &lt 0.01). The incidence of preterm delivery due to sudden massive bleeding and the amount of bleeding during cesarean section were significantly higher in type A + S and type A + S with lacunae, respectively. Conclusions: Sonographic EFS in the lower edge of the placenta overlying the cervix indicates the risk of sudden massive antepartum bleeding. Furthermore, lacunae with sponge-like echo may also reflect the risk of massive bleeding at cesarean section. These findings warrant further observational studies to verify their clinical implications. Copyright © 2002 S. Karger AG, Basel.

OBJECTIVES: To detect the cervical gland area in threatened preterm labor, and to determine its detection rate and relationship with cervical maturation and outcome of pregnancy in preterm labor. METHODS: This was a mixed longitudinal and cross-sectional study involving 615 transvaginal scans performed to detect the cervical gland area and measure cervical length in 101 singleton pregnancies with threatened preterm labor. The patients were treated with intravenous administration of ritodrine chloride for regular uterine contractions at 16-35 weeks of gestation. 260 normal singleton pregnancies served as controls. Simultaneously conventional digital examination was used to assess the cervical maturation index. The detection rates of the cervical gland area, measurements of cervical length by sonography, and assessment of the cervical maturation index by digital examination in threatened preterm labor were compared with those of normal singleton pregnancies. In the threatened labor group, the outcome of pregnancy was assessed according to the sonographic absence or presence of the cervical gland area. RESULTS: In the normal pregnancy group, the detection rate of the cervical gland area remained practically constant until the 31st week of pregnancy (97%), but substantially decreased thereafter (70.2% in gestational weeks 32-35). In the threatened preterm labor group, the detection rate of the cervical gland area was constantly lower (44.5%) and the cervical maturation index was higher (4.65 score) than in the normal pregnancy group (83.1% and 1.80 score, respectively). The outcome of pregnancy in the threatened preterm labor group was poorer in the subgroup with the absence of a cervical gland area than in the subgroup with the presence of a cervical gland area (duration of pregnancy 257.0 vs. 271.0 days, birth weight 2,597.2 vs. 2,990.0 g, and admission to delivery interval 38.8 vs. 60.8 days). Highly significant correlations were noted among the detection rates of a cervical gland area and cervical length, cervical maturation index, and outcome of pregnancy. CONCLUSIONS: This study demonstrates for the first time that the sonographic absence of the cervical gland area reflects cervical maturation and could be considered as a predictor of threatened preterm labor and a sign of poor outcome of pregnancy in this condition.

Endometrial cancer is believed to have a better prognosis than cervical cancer. However, this is not necessarily true for cases beyond International Federation of Gynecology and Obstetrics (FIGO) stage III, and advanced endometrial cancer with distant metastases in particular has a poor prognosis. Moreover, there is no established therapy for advanced endometrial cancer. Recently, we treated two patients with endometrial cancer with multiple lung metastases (FIGO stage IVb). Both patients had massive uncontrollable genital bleeding and eventually progressed to anemia. The imminent severe bleeding was considered to be a major reason for exacerbation of their general condition. Therefore, hysterectomy was performed as a counter-measure to improve their general condition. In their postoperative course, the two patients successfully under-went T-J chemotherapy [paclitaxel: 210m/m2 over 3h carboplatin: area under the curve (AUC) 5]. Six courses of the regimen were given every 3-4 weeks. Multiple lung shadows in chest X-P and computed tomography (CT) were reduced in number and size after two courses of T-J chemotherapy. The multiple lung metastases either disappeared or just remained as scars after six courses. There has been no evidence of recurrence for 28 months in one patient and 7 months in the other patient.

Objectives: To detect the cervical gland area during normal pregnancy, and to determine its detection rate and relationship with cervical maturation. Design: This was a mixed longitudinal and cross-sectional sonographic study involving a total of 514 transvaginal scans performed for detection of cervical gland area and measurement of cervical length in 260 normal singleton pregnancies at 16-41 weeks of gestation. The conventional cervical maturation index was measured simultaneously by digital examination. Results: The detection rate of cervical gland area remained practically constant until the 31st week of pregnancy, but significantly decreased thereafter. Highly significant correlations were noted between the detection rate of cervical gland area and cervical length, cervical gland area and cervical maturation index, and cervical length and cervical maturation index. Conclusions: This study showed for the first time that cervical gland area can be detected sonographically and that its absence might be a predictor of preterm labor.