Codon-specific translational defect caused by a wobble modification deficiency in mutant tRNA from a human mitochondrial disease.

Point mutations in the mitochondrial (mt) tRNA(Leu(UUR)) gene are responsible for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), a subgroup of mitochondrial encephalomyopathic diseases. We previously showed that mt tRNA(Leu(UUR)) with an A3243G or T3271C mutation derived from patients with MELAS are deficient in a normal taurine-containing modification (taum5U; 5-taurinomethyluridine) at the anticodon wobble position. To examine decoding disorder of the mutant tRNA due to the wobble modification deficiency independent of the pathogenic point mutation itself, we used a molecular surgery technique to construct an mt tRNA(Leu(UUR)) molecule lacking the taurine modification but without the pathogenic mutation. This "operated" mt tRNA(Leu(UUR)) without the taurine modification showed severely reduced UUG translation but no decrease in UUA translation. We thus concluded that the UUG codon-specific translational defect of the mutant mt tRNAs(Leu(UUR)) is the primary cause of MELAS at the molecular level. This result could explain the complex I deficiency observed clinically in MELAS.

Ultrasonographic and clinical appearance of hemorrhagic ovarian cyst diagnosed by transvaginal scan.

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.

Value of ultrasonography in the diagnosis of placental abruption.

Placental abruption is a serious cause of fetal mortality. We retrospectively reviewed 24 patients with placental abruption who underwent cesarean section to evaluate ultrasonographic images with reference to the clinical findings and fetal and maternal prognosis. Fourteen of these patients presenting with placental edge separation and persistent hematoma showed a significantly smaller area of abruption, a smaller amount of intraoperative bleeding, a smaller incidence of disseminated intravascular coagulation, and a higher Apgar score as compared to the 10 patients with a thickened placenta. The patients with thickened placenta tended to have a typical clinical presentation, whereas those with placental edge separation and hematoma appeared to have an atypical and mild clinical manifestation. It was concluded that ultrasonography is useful in the diagnosis of mild and atypical placental abruption.

Serum leptin concentration in young adult women with ovulatory dysfunction.

To investigate the functional role of leptin in human ovulation, we measured serum leptin, LH, FSH and estradiol in 16 young adult women suffering from ovulatory dysfunction with BMI ranging from 17.5 to 24.5 (group A). The control subjects included 12 women with regular ovulation and matched age and BMI (group B). We found that serum leptin concentration in group A subjects was significantly lower than that in group B subjects (4.1+/-0.5 vs. 6.1+/-0.4 ng/ml, p<0.01). The percent body fat, estradiol, LH and FSH concentrations in groups A and B were not significantly different. These results indicate that anovulatory young adult women have lower leptin concentration than women with regular ovulation, thus suggesting a key role for leptin in regular ovulation or ovulatory dysfunction.

Determination of blastocyst implantation site in spontaneous pregnancies using three-dimensional transvaginal ultrasound.

Three-dimensional transvaginal ultrasound was used to determine the location of early gestational sacs (E-GSs) and, as a result, the physiological implantation sites of human blastocysts. We examined 138 patients who were found by three-dimensional transvaginal ultrasound to have a GS with an inner diameter of 3 to 6 mm (E-GS). The uterine cavity was divided into three parts: upper, middle, and lower regions. The upper region was subdivided into the right, middle, and left areas, and the middle region was subdivided into the right and left areas. Thus, overall 6 areas were designed and the frequency of the E-GS detection in each area was evaluated. Of the 138 patients, 123 (89.1%) had E-GSs detected in the upper region, which was found to be the most frequent region. When the frequency of E-GS detection among the upper three areas was compared, the right and left upper areas had a higher frequency than the middle upper area. As to the miscarriage rate, patients with E-GSs detected in the upper region had a significantly lower rate than those in the middle and lower regions (p<0.05). The endometrium suitable for human blastocyst implantation under physiological conditions is at the uterine fundus, especially near the uterotubal junction.

Is transvaginal ultrasonography at mid-trimester useful for predicting early spontaneous preterm birth?

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.

Assessment of fallopian tube cytology for the diagnosis of endometriosis and hydrosalpinx.

Fallopian tube cytology has been used as a useful tool in the diagnosis of infertility. In this study, we developed an intra-fallopian tube cell collection method with the simultaneous use of a laparoscope and hysteroscope, and examined its safety and applicability for the diagnoses of endometriosis and hydrosalpinx. Fallopian tube cells were collected at laparoscopy and hysteroscopy from 20 volunteer patients who visited the infertility clinic. There were 10 patients with normal fallopian tubes (Group 1), 7 with pelvic endometriosis (Group 2), and 3 with hydrosalpinx (Group 3). The collected cells were fixed onto glass slides using an auto-smear method, stained by the Papanicolaou method and subjected to detailed cytomorphological examinations. In each case, an adequate number of cells with well-preserved morphology for a reliable evaluation was obtained. Cells from normal fallopian tubes were mainly fallopian tube epithelial cells including ciliated columnar cells and secretory cells. The number of inflammatory cells was quite low. A characteristic feature in cases with pelvic endometriosis was the presence of a large number of macrophages, some of which showed hemosiderin phagocytosis. In contrast, cases with hydrosalpinx showed an extremely low cellular component. No complications were found in any of the patients. Our study indicates that the present intra-fallopian tube cell collection method using a laparoscope and hysteroscope is a reliable and safe method that can be applied to the diagnosis of endometriosis, hydrosalpinx, as well as pelvic infertility.

Anticipation of uterine bleeding in placenta previa based on vaginal sonographic evaluation.

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 < 0.01). The risk of antepartum massive bleeding was also significantly higher in type C (p < 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.

Detection of the cervical gland area in threatened preterm labor using transvaginal sonography in the assessment of cervical maturation and the outcome of pregnancy.

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.