[A Case Report of Surgery and Chemotherapy for a Patient with Rapidly Progressing Breast Cancer during Pregnancy].

A 33-year-old woman became aware of a right breast mass at her 28th week of pregnancy. From the biopsy results, we diagnosed her with right breast cancer. At her 33rd week of pregnancy, she underwent modified radical mastectomy (pT2N3aM0, Stage III C, ER-negative, PR-negative, HER2-positive), and she elected to receive adjuvant therapy after the surgery during her pregnancy. She received the first course of EC (epirubicin plus cyclophosphamide) therapy on the 13th postoperative day (35 weeks of gestation) and gave a natural, vaginal delivery at 36 weeks and 5 days of gestation. On the 4th day after birth, the patient noticed a contralateral left breast mass and was diagnosed with left breast cancer, after core needle biopsy. She received 4 courses of EC therapy and is currently undergoing PTX plus HER (paclitaxel plus trastuzumab) therapy. Regarding chemotherapy during pregnancy, we recommend that there is no need to perform artificial preterm birth, because chemotherapy has little influence on children after their second-trimester. After the second-trimester, chemotherapy can be safely performed.

Footprints of New Strong Dynamics via Anomaly and the 750 GeV Diphoton.

The chiral anomaly provides smoking-gun evidence of a new confining gauge theory. Motivated by a reported event excess in a diphoton invariant mass distribution at the LHC, we discuss a scenario that a pseudo-Nambu-Goldstone (PNG) boson of a new QCD-like theory is produced by gluon fusion and decays into a pair of the standard model gauge bosons. Despite the strong dynamics, the production cross section and the decay widths are determined by an anomaly matching condition. The excess can be explained by the PNG boson with mass of around 750 GeV. The model also predicts exotic hadrons such as a color-octet scalar and baryons. Some of them are within the reach of the LHC experiment.

[Reinforcement of warfarin action in a patient administered S-1].

A case showing reinforcement of the action of warfarin and potassium in a patient administered S-1 is reported.The patient was a 71-year-old man with left upper gingival cancer.He had ventricular tachycardia (VT), hypertrophic cardiomyopathy, and a cerebellar infarction.He underwent a pacemaker implantation, and was administered warfarin.After the operation, in mid-March 2010, he was administered with S-1 and warfarin. However, the international normalized ratio of prothrombin time (PT-INR) increased to an extremely high level of 5.82, and S-1 and warfarin were stopped. They were re-administered at the end of April, and the PT-INR stabilized to approximately 2.

Maternal dietary patterns in pregnancy and fetal growth in Japan: the Osaka Maternal and Child Health Study.

Maternal nutritional status during pregnancy is an important determinant of fetal growth. Although the effects of several nutrients and foods have been well examined, little is known about the relationship of overall maternal diet in pregnancy to fetal growth, particularly in non-Western populations. We prospectively examined the relationship of maternal dietary patterns in pregnancy to neonatal anthropometric measurements at birth and risk of small-for-gestational-age (SGA) birth among 803 Japanese women with live-born, singleton, term deliveries. Maternal diet in pregnancy was assessed using a validated, self-administered diet history questionnaire. Dietary patterns from thirty-three predefined food groups (g/4184 kJ) were extracted by cluster analysis. The following three dietary patterns were identified: the 'meat and eggs' (n 326), 'wheat products', with a relatively high intake of bread, confectioneries and soft drinks (n 303), and 'rice, fish and vegetables' (n 174) patterns. After adjustment for potential confounders, women in the 'wheat products' pattern had infants with the significantly lowest birth weight (P = 0·045) and head circumference (P = 0·036) among those in the three dietary patterns. Compared with women in the 'rice, fish and vegetables' pattern, women in the 'wheat products' pattern had higher odds of having a SGA infant for weight (multivariate OR 5·2, 95 % CI 1·1, 24·4), but this was not the case for birth length or head circumference. These results suggest that a diet high in bread, confectioneries, and soft drinks and low in fish and vegetables during pregnancy might be associated with a small birth weight and an increased risk of having a SGA infant.

A case of serous endometrial intraepithelial carcinoma with p53 positivity for six years.

A 69-year-old postmenopausal woman was referred because she had been taking tamoxifen for four years. Tissues obtained by endometrial curettage were immunopositive for p53, but there was no definite malignancy. At age 73, cytology again showed abnormalities, so we repeated complete endometrial curettage. Again, there was no malignancy, but p53 immunostaining was widely positive. At age 75, hysterectomy was performed because cytological examination showed increasingly abnormal findings and the patient opted for surgery. In the resected uterus, endometrial glands were replaced by malignant cells resembling papillary serous carcinoma cells with high-grade nuclei, but there was no stromal or myometrial invasion. The pathological diagnosis was intraepithelial serous endometrial carcinoma. This is a rare case because we could follow the patient for 6 years by endometrial cytology or endometrial curettage and we observed gradual transformation into endometrial intraepithelial carcinoma.

Effects of 4-hydroxy-2-nonenal, a major lipid peroxidation-derived aldehyde, and N-acetylcysteine on the cyclooxygenase-2 expression in human uterine myometrium.

BACKGROUND: Chorioamnionitis is one of the important causes of preterm labor. Preterm labor with chorioamnionitis is associated with oxidative stress. We reported that 4-hydroxy-2-nonenal (4-HNE), a major end product of oxidative fatty acid metabolism, is accumulated in the placenta with chorioamnionitis. The aim of this study was to confirm the effect of 4-HNE on cyclooxygenase-2 (COX-2) and prostaglandin (PG) induction in the uterine myometrial tissues. We also examined the effect of N-acetylcysteine (NAC) on 4-HNE-induced COX-2 expression. METHODS: Uterine myometrial tissues were obtained from 5 patients. One of them underwent elective cesarean section without labor, and 4 of them underwent hysterectomy because of placental previa or atonic bleeding. We stimulated the uterine myometrial tissues with 4-HNE. In addition, the tissues were pretreated with NAC before 4-HNE treatment. The expression of COX-2 mRNA was observed by real-time PCR. PGE2 and prostacyclin release into the supernatants of the tissue cultures was measured by ELISA. RESULTS: 4-HNE induced the COX-2 mRNA expression and PGE2 production in the uterine myometrial tissue culture in a dose-dependent and time-dependent manner. NAC inhibited 4-HNE-induced COX-2 expression. CONCLUSION: 4-HNE may play an important role in preterm labor. NAC might be protective against preterm labor under oxidative stress.

Change of salivary stress marker concentrations during pregnancy: maternal depressive status suppress changes of those levels.

AIM: The aim of the present study was to show changes in salivary cortisol and chromogranin A/protein concentrations as stress markers during pregnancy and to clarify the effect of chronic stress on stress markers. MATERIAL AND METHODS: Salivary samples were collected from 69 pregnant women during pregnancy. Salivary cortisol levels and chromogranin A/protein titers were determined. We surveyed the women's chronic stress using the Zung self-rating depression scale and General Health Questionnaire-28. RESULTS: Cortisol levels in the saliva of pregnant women showed biphasic change during pregnancy. Chromogranin A/protein levels in the saliva of pregnant women increased in the second and the early third trimesters and decreased to the puerperal period. Salivary cortisol concentrations of the chronic high stress group were significantly lower compared with those of the normal group. Salivary chromogranin A/protein concentrations of the chronic high stress group were also significantly lower than those of the normal group. CONCLUSION: The titration of salivary cortisol concentrations and chromogranin A/protein levels is a useful tool to determine maternal stress levels. The elevation of cortisol and chromogranin A/protein in the saliva was suppressed in the chronic high stress group during pregnancy.

Light dark photon dark matter from inflation.

We discuss the possibility of producing a light dark photon dark matter through a coupling between the dark photon field and the inflaton. The dark photon with a large wavelength is efficiently produced due to the inflaton motion during inflation and becomes non-relativistic before the time of matter-radiation equality. We compute the amount of production analytically. The correct relic abundance is realized with a dark photon mass extending down to 10 -21 eV.

Uterine artery flow velocity waveforms during uterine contractions: differences between oxytocin-induced contractions and spontaneous labor contractions.

AIM: To clarify the effects on uterine arterial flow velocity waveforms of uterine contractions following oxytocin infusion and during spontaneous labor. METHODS: Uterine arterial flow velocity waveforms were obtained by pulsed Doppler methods from 22 women during an oxytocin challenge test (OCT), 26 women during oxytocin-induced labor, and 40 women during spontaneous labor. Mean resistance index (RI) for bilateral arteries was used for analyses. After the onset of labor, flow velocity waveforms were assessed according to cervical dilatation. During OCT, Doppler flow velocimetry was performed when three uterine contractions occurred per 10-min period. RESULTS: RI values did not differ significantly between induced and spontaneous labor during relaxations at any level of cervical dilatation. However, during contractions, RI was significantly higher for induced labor than for spontaneous labor. Absence or reversal of flow was more frequent in the OCT group than in the induced labor group (P < 0.0001). However, no significant differences were found between spontaneous and induced labor groups. CONCLUSION: Interactions between the contracting uterine body and the relaxing lower segment in oxytocin-induced labor might be associated with differences in uterine arterial flow during contraction between oxytocin-induced and spontaneous labor. However, changes in the intensity of uterine contractions during labor progression might differ between oxytocin-induced and spontaneous labor.

Acceleration time of fetal arterial blood flow velocity waveforms: a preliminary study.

BACKGROUND: Doppler ultrasonography has been widely used for fetal estimation, but most of them were estimated by the resistance and pulsatility indices. Acceleration time is one of parameters of flow velocity waveforms, but only few reports had discussed acceleration time of fetal circulation. METHODS: We analyzed Doppler flow velocity waveforms of fetal middle cerebral artery, descending aorta and abdominal umbilical artery obtained from 70 normal pregnant women between 18 and 40 weeks. Acceleration time was cross-sectionaly examined throughout pregnancy course. RESULTS: The acceleration times revealed no remarkable changes throughout pregnancy course in the middle cerebral artery, but significant increases were observed in the acceleration time of the descending aorta between 18-23 and 24-32 weeks. It also significantly decreased after 33 weeks compared to that of 18-32 weeks in the umbilical artery. CONCLUSIONS: The acceleration time in fetal descending aorta is significantly shorter than that in the abdominal umbilical artery between 18 and 32 weeks of gestation. The umbilical arterial acceleration time apparently decreases throughout pregnancy course. Its values are almost double for that in the descending aorta between 18 and 23 weeks, but it becomes to be equal to the aortic acceleration time. The continuous decrease of the umbilical arterial acceleration time might be a result of a relative increase of placental flow.

Computer-based screening of chest X-rays for vertebral compression fractures as an osteoporosis index in men.

We evaluated the recognition of osteoporosis in the veteran male population through a computer-based review of chest X-ray (CXR) reports in the Veterans Affairs Northern California Health Care System database, looking for unrecognized vertebral fractures. All CXR reports between January 1, 2000 and December 31, 2001, were scanned for the terms "compression" or "wedg (where the "" indicates a wild card search encompassing such terms as "wedge" or "wedging")". During this time, 26,994 CXR examinations were performed on 18,069 patients. 22,494 (83.3% of the total) CXR examinations were done in 14,561 men >or=50 years of age. 780 CXR reports (3.5%) encompassing 664 men (4.5%) contained at least one key phrase suggesting osteoporosis. Three years later, 495 of these 664 men were still living. 99 of these (20%) had been diagnosed with osteoporosis, 72 (15%) had a dual-energy X-ray absorptiometry (DXA) scan, and 89 (18%) had ever been prescribed a bisphosphonate. Overall, only 126 (25%) men had chart documentation indicating some recognition by the provider of the abnormality reported on CXR. We conclude that a significant fraction of men >50 years old may have unrecognized osteoporosis severe enough to result in vertebral fracture. We conclude that computerized screening of CXR reports may represent an effective strategy to aid clinicians in identifying men at risk for further debilitating fractures.

Protein S deposition at placenta: a possible role of protein S other than anticoagulation.

Protein S is an antithrombotic cofactor for protein C that also has multifunctional anti-inflammatory, cellular protective, apoptotic and mitogenic properties. Protein S levels are thought to decrease during pregnancy, but the underlying mechanism remains unknown. We compared protein S concentrations throughout normal pregnancy with those of nonpregnant women and measured plasma C4b-binding protein levels in nonpregnant women and in pregnant women at the 40th gestational week. We also examined protein S and C4b-binding protein in the placenta by immunohistochemical staining at early (20th gestational week) and late (40th gestational week) stages of pregnancy. Plasma protein S activity and free protein S-antigen levels significantly decreased from the 10th gestational week and total protein S antigen decreased from the 20th. C4b-binding protein levels between pregnant and nonpregnant women did not significantly differ. The stainable portion of protein S was located at the fetomaternal interface, particularly at degenerative villi. C4b-binding protein was weakly stained at the same areas as protein S. Neither protein S nor C4b-binding protein were stained at normal villi. These results indicated that protein S can protect or restore damaged villi via a physiological effect in addition to its anticoagulation properties.

Beverage consumption and the prevalence of tooth loss in pregnant Japanese women: the Osaka Maternal and Child Health Study.

Recently, there has been growing interest in the impact of beverage consumption on dental health because changes have occurred in the types and quantities of beverage consumed. This cross-sectional study investigated the relationship between consumption frequencies of various beverages and the prevalence of tooth loss among young adult women. Study subjects were 1002 pregnant Japanese women. Tooth loss was defined as previous extraction of one or more teeth. Dietary habits were evaluated by a validated dietary history questionnaire. Logistic regression analysis was used to estimate the odds ratios and their 95% confidence intervals of tooth loss. Adjustment was made for age, gestation, parity, cigarette smoking, passive smoking at home and at work, family income, education, changes in diet in the previous one month, season when data were collected and body mass index. Of the 1002 subjects, 256 women had lost one or more teeth. Coffee consumption was independently associated with an increased prevalence of tooth loss. When subjects were divided according to consumption of coffee with or without sugar, an increased prevalence of tooth loss was found only in subjects who consumed coffee without addition of sugar. Compared with the lowest consumption of green tea, the intermediate but not the highest consumption of green tea was associated with an increased prevalence of tooth loss. There was no measurable association of intake of milk, black tea, cola, or 100% fruit juice with the prevalence of tooth loss. The findings suggest that coffee consumption might be associated with an increased prevalence of tooth loss among young adult women.

Quantitative analysis of sensitivity to a Wnt3a gradient in determination of the pole-to-pole axis of mitotic cells by using a microfluidic device.

Proper determination of the cell division axis is essential during development. Wnt3a is a known regulator of the cell division axis; however, the sensitivity of cells to Wnt3a signalling and its role in determining the cell division axis have not been measured to date. To address this gap, we took advantage of the asymmetric distribution of outer dense fibre 2 (ODF2/cenexin) proteins on centrosomes in dividing cells. To precisely quantify the sensitivity of cells to Wnt3a signalling, we developed a microfluidic cell culture device, which can produce a quantitative gradient of signalling molecules. We confirmed that mitotic SH-SY5Y neuroblastoma cells could detect a 2.5 ~ 5 × 10-3 nm·µm-1 Wnt3a concentration gradient and demonstrated that this gradient is sufficient to affect the determination of the pole-to-pole axis of cell division during the later stages of mitosis.

Effects of different sampling points on evaluation of fetal descending aortic flow.

BACKGROUND: Widespread use of fetal aortic blood flow velocity measurements for assessment of fetal circulatory status has been precluded by difficulties in achieving an adequate Doppler insonation angle at particular sampling points. The goal of this study was to evaluate the differences in resistance index (RI) and systolic peak velocity (Vmax) of fetal aortic blood flow velocity waveforms throughout gestation among various Doppler sampling points. METHODS: A total of 551 normal women between 18-41 weeks of pregnancy participated in this study. Pulsed Doppler flow velocity waveforms were acquired from three different aortic sampling points (thoracic portion, beneath the diaphragm, and abdominal portion) of the fetal descending aorta. The Vmax and RI were calculated at the respective sampling points. RESULTS: The Vmax were significantly lower in abdominal portion than those in thoracic portion at every time point (from 69 +/- 11 cm/second in thoracic to 49 +/- 8 cm/second in abdominal portion at 18-19 gestational weeks, p<0.0001), and RI were also lower (from 0.84 +/- 0.05 in thoracic portion to 0.76 +/- 0.05 in abdominal portion at 18-19 gestational weeks, p<0.0001). Significant increase in the Vmax was seen until third trimester (from 58+/-10 cm/second at 18-19 gestational weeks to 113 +/- 13 cm/second at 38-39 gestational weeks beneath the diaphragm, p<0.0001), while the RI remained stable (0.79 +/- 0.04 at 18-19 gestational weeks; 0.80 +/- 0.05 at 38-39 gestational weeks beneath the diaphragm). CONCLUSIONS: In measuring the fetal circulatory status, these data demonstrate that the sampling point should be considered when evaluating the maximum systolic velocity and the resistance index of the fetal descending aorta.

Detection of Temperature Difference in Neuronal Cells.

For a better understanding of the mechanisms behind cellular functions, quantification of the heterogeneity in an organism or cells is essential. Recently, the importance of quantifying temperature has been highlighted, as it correlates with biochemical reaction rates. Several methods for detecting intracellular temperature have recently been established. Here we develop a novel method for sensing temperature in living cells based on the imaging technique of fluorescence of quantum dots. We apply the method to quantify the temperature difference in a human derived neuronal cell line, SH-SY5Y. Our results show that temperatures in the cell body and neurites are different and thus suggest that inhomogeneous heat production and dissipation happen in a cell. We estimate that heterogeneous heat dissipation results from the characteristic shape of neuronal cells, which consist of several compartments formed with different surface-volume ratios. Inhomogeneous heat production is attributable to the localization of specific organelles as the heat source.

In situ measurement of CO2 and water vapour isotopic compositions at a forest site using mid-infrared laser absorption spectroscopy.

We conducted continuous, high time-resolution measurements of CO2 and water vapour isotopologues ((16)O(12)C(16)O, (16)O(13)C(16)O and (18)O(12)C(16)O for CO2, and H2(18)O for water vapour) in a red pine forest at the foot of Mt. Fuji for 9 days from the end of July 2010 using in situ absorption laser spectroscopy. The δ(18)O values in water vapour were estimated using the δ(2)H-δ(18)O relationship. At a scale of several days, the temporal variations in δ(18)O-CO2 and δ(18)O-H2O are similar. The orders of the daily Keeling plots are almost identical. A possible reason for the similar behaviour of δ(18)O-CO2 and δ(18)O-H2O is considered to be that the air masses with different water vapour isotopic ratios moved into the forest, and changed the atmosphere of the forest. A significant correlation was observed between δ(18)O-CO2 and δ(13)C-CO2 values at nighttime (r(2)≈0.9) due to mixing between soil (and/or leaf) respiration and tropospheric CO2. The ratios of the discrimination coefficients (Δa/Δ) for oxygen (Δa) and carbon (Δ) isotopes during photosynthesis were estimated in the range of 0.7-1.2 from the daytime correlations between δ(18)O-CO2 and δ(13)C-CO2 values.

Angioleiomyoma of the cheek: a case report.

Angioleiomyoma is a form of subcutaneous vascular leiomyoma that usually occurs in the extremities. Leiomyoma of the oral cavity represents only 0.4% of soft tissue neoplasms and 0.06% of leiomyomas. Isolated cases of angioleiomyoma have been reported in the knee and lower thigh, gastrointestinal tract, genital and renal tract, and brain. Histopathologic examination by biopsy is necessary to establish a diagnosis, and immunohistochemical staining, along with conventional hematoxylin-eosin staining, is important. The differential diagnosis includes hemangioma and angiosarcoma. At present, surgical resection is the standard therapy for leiomyoma, and recurrence is extremely rare. We report a rare case of angioleiomyoma of the cheek in a 45-year-old man. The postoperative course was uneventful, without complications.

High-speed microscopy with an electrically tunable lens to image the dynamics of in vivo molecular complexes.

We provide an evaluation for an electrically tunable lens (ETL), combined with a microscope system, from the viewpoint of tracking intracellular protein complexes. We measured the correlation between the quantitative axial focus shift and the control current for ETL, and determined the stabilization time for refocusing to evaluate the electrical focusing behaviour of our system. We also confirmed that the change of relative magnification by the lens and associated resolution does not influence the ability to find intracellular targets. By applying the ETL system to observe intracellular structures and protein complexes, we confirmed that this system can obtain 10 nm order z-stacks, within video rate, while maintaining the quality of images and that this system has sufficient optical performance to detect the molecules.

Activity of synthetic enzymes of tetrahydrobiopterin in the human placenta.

Tetrahydrobiopterin (BH4) is an essential co-factor for nitric oxide (NO) synthase (NOS) and regulates the production of NO, or endothelium-derived relaxation factor. Although NOS is highly expressed in the placenta and NO plays a critical role in the regulation of feto-placental circulation, the mechanism maintaining the level of BH4 is not known. To investigate the de novo synthesis of BH4 in the human placenta, the activity of guanosine triphosphate cyclohydrolase I (GTPCH), 6-pyruvoyltetrahydropterin synthase (PTPS), and sepiapterin reductase (SR) in the chorionic tissue during the first, second and third trimester of pregnancy was analyzed. GTPCH activity was the lowest of the three enzymes and became negligible after the second trimester. There was no significant change in PTPS activity throughout pregnancy. Although SR activity decreased significantly after the second trimester, the levels remained abundant throughout pregnancy. These results showed that GTPCH is a rate-limiting enzyme and the total activity of the de novo synthesis of BH4 is negligible in the mature placenta after the second trimester when fetal growth is accelerated. The present study suggests that the level of BH4 in the placenta depends principally on the system other than de novo synthesis. The salvage pathway is considered the most potent system, which is formed by the transfer of the substrates from the fetus and their enzymatic conversion to BH4 in the placenta.