Literatura académica sobre el tema "E178.1 .p4 2001"

Abstract Progesterone (P4) plays a central role in normal uterine function, from embryo implantation in endometrium to establishment and maintenance of uterine quiescence during pregnancy in the myometrium. Considering its diverse physiological effects on female reproductive function, rather little is known about downstream events of P4 action. Recent progress in differential screening technologies facilitated identification of such inducible genes. We used uteri of wild-type and progesterone receptor null mutant mice as a starting material and screened for differentially expressed genes by medium-density cDNA expression array. Here, we report that the expression of the morphogen, Indian hedgehog (Ihh), is rapidly stimulated by P4 in the mouse uterus. The level of Ihh mRNA is induced within 3 h, after a single administration of P4 to ovariectomized mice. The induced Ihh mRNA and protein were localized to the luminal and glandular epithelial compartment of the endometrium. During pseudopregnancy, the Ihh mRNA level was transiently increased in the preimplantation period and d 3 and d 4 post coitum and then decreased rapidly at d 5 post coitum. Furthermore, the expression profile of patched-1, hedgehog interacting protein-1, and chicken ovalbumin upstream promoter-transcription factor II, genes known to be in the hedgehog signaling pathway in other tissues, followed the expression pattern of Ihh during the periimplantation period. Our results suggested that Ihh is regulated by P4, and the Ihh signaling axis may play a role in the preparation of the uterus for implantation during the periimplantation period.

Among inositol phosphate kinases, Ins(3,4,5,6)P4 1-kinase has been considered to be an outsider with disparate sequence, a proclaimed capacity to also phosphorylate proteins and apparent 1-phosphatase activity. Such multifunctionality, coupled with ignorance of its operational domains, complicates any mechanistic rationale behind literature reports that Ins(3,4,5,6)P4 1-kinase regulates apoptosis, salt and fluid secretion, and transcription. We have expressed poly(His)-tagged human Ins(3,4,5,6)P4 1-kinase in Sf9 insect cells and purified the enzyme using Ni–agarose chromatography. Protein kinase activity was eluted from the Ni–agarose column, but this did not co-elute with the Ins(3,4,5,6)P4 1-kinase, indicating that the protein kinase and inositol kinase activities belong to separate proteins. To pursue this conclusion, we prepared catalytically inactive mutants of the Ins(3,4,5,6)P4 1-kinase by identifying and targeting the ATP-binding site. Our strategy was based on sequence alignments suggesting homology of the Ins(3,4,5,6)P4 1-kinase with ATP-grasp metabolic enzymes. Individual mutation of four candidate MgATP-binding participants, Lys157, Asp281, Asp295 and Asn297, severely compromised Ins(3,4,5,6)P4 1-kinase activity. Yet, these mutations did not affect the protein kinase activity. We conclude that the Ins(3,4,5,6)P4 1-kinase is not a protein kinase, contrary to earlier reports [e.g. Wilson, Sun, Cao and Majerus (2001) J. Biol. Chem. 276, 40998–41004]. Elimination of protein kinase activity from the enzyme's repertoire and recognition of its ATP-grasp homology together indicate that structural, functional and catalytic relationships between Ins(3,4,5,6)P4 1-kinase and other inositol phosphate kinases are closer than previously thought [Gonzalez, Schell, Letcher, Veprintsev, Irvine and Williams (2004) Mol. Cell 15, 689–701].

8078 Background: Treatment of metastatic non-small cell lung cancer (NSCLC) has evolved over the last decade with the increased use of third-generation chemotherapy agents, established benefits from second-line chemotherapy, and the development of targeted agents. We conducted a study to evaluate whether these treatment advances translated into improved survival in a large registry database. Methods: The Surveillance Epidemiology and End Results (SEER) registry was queried for patients with NSCLC stage IV, aged 21 or older, and diagnosed between 1990 and 2005. Overall Survival (OS) rates were estimated by the Kaplan-Meier method and compared using log-rank test. Cox proportional hazard model was fitted to evaluate whether the diagnostic period is an independent predictor for OS. Demographic variables included period of diagnosis (1990–1993 or P1, 1994–1997 or P2, 1998–2001 or P3, and 2002–2005 or P4), age, gender, race, and histology. Results: There were 127,816 patients meeting eligibility criteria. Median age at presentation was 67 and most patients were male (58%), white (81%), and had adenocarcinoma (39%). Although there was no significant differences in OS between periods 1 and 2 (p = 0.18), there was a significant improvement from periods 2 to 3 (p < 0.001) and 3 to 4 (p < 0.001). 1-y and 2-y OS increased from 13.2% and 4.5% respectively in P1 to 19.4% and 7.8% respectively in P4. Predictive factors for improved survival in multivariate analyses included diagnostic period (p < 0.001), younger age (p < 0.0001), female gender (p < 0.0001), and non-black race (p < 0.0001). After adjusting for demographic factors, there were no significant differences in OS between adenocarcinoma and squamous cell from P1 to P3 (1990–2001). However, P4 showed a significant increase in OS for adenocarcinoma compared with squamous cell (p = 0.02). Conclusions: There has been a significant improvement in OS for stage IV NSCLC over the last 8 years. The recent differences in outcomes based on histology observed in P4 may reflect the increased activity of newer therapies in adenocarcinoma compared with squamous cell, including gefitinib and erlotinib. No significant financial relationships to disclose.

In beef cattle, 20 to 44% embryonic loss occurs during the early stages of pregnancy (Humblot et al. 2001). However, the mechanism of early and late embryonic death is not clear. We investigated occurrence of embryonic death by monitoring ovarian hormones dynamics and checking for the presence of the conceptus after artificial insemination or embryo transfer in beef cattle. Twenty Japanese black females were inseminated (AI) and 12 females were transferred with 1 embryo (ET). Blood samples were collected on Days 21, 24, 28, 38, 48, 58, and 68 post-oestrus (oestrus = Day 0) and then stored at –30°C. Progesterone (P4) and oestradiol (E2) plasma concentrations were analysed using a chemiluminescent immunoassay. On each day of blood sampling, ovaries and presence of a conceptus in the uterus were monitored by ultrasonography. At Day 24 post-oestrus, the presence of the fetus was detected in 8 females (AI, n = 6; ET, n = 2), whereas only 3 females were confirmed to be pregnant at Day 28 and Day 38 post-oestrus. No embryo loss was seen at later stages of pregnancy (Days 48, 58, and 68 post-oestrus). At Day 21 post-oestrus, the conceptus could not be detected by ultrasonography but the E2/P4 ratio provided indication on the pregnancy status of the females that were classified as pregnant (n = 8) or not pregnant (n = 24) at day 24 post-oestrus (1.7 ± 2.2 versus 28.0 ± 34.2 respectively; mean ± s.d.). In the nonpregnant females compared with the pregnant ones at Day 24 post-oestrus, P4 declined below 1 ng mL–1 (0.6 ± 0.2 ng mL–1 v. 8.6 ± 3.9 ng mL–1), whereas E2 blood level remained stable (15.7 ± 21.9 v. 18.1 ± 1.1 pg mL–1). The decrease in P4 levels led to an increase in E2/P4 ratio (1.3 to 37.3 on Day 24). Our study suggests that a large proportion of embryo loss (75%) occurs before Day 24, whereas an additional 16% loss was seen between Day 24 and Day 28 post-oestrus. This embryo loss was shown to be associated with the altered balance of ovarian hormones.

The importance of serum progesterone (P4) during the first weeks of pregnancy to reduce the embryo mortality in cattle herds has been demonstrated (Mann and Lamming 2001 Reproduction 121, 175-180). Studies show that a P4 peak at the beginning of pregnancy (about 5 days after the natural breeding or AI) helps development of the concept via secretion of interferon-τ (Mann 2002 XXII World Buiatrics Congress 18-23, 300-306). Studies have shown that the administration of gonadotropin-releasing hormone (GnRH) or its agonists after AI may stimulate corpus luteum function, induce the formation of an accessory corpus luteum, or increase of P4 serum concentrations and, therefore, improve embryonic survival (Bartolome et al. 2005 Theriogenology 63, 1026-1037). This work aims to evaluate the effect of GnRH injection 12 d after fixed-time AI(FTAI) on P4 serum levels and pregnancy rate of beef crossbred cows. The cows (Bos taurus indicus × Bos taurus taurus, n = 59), range in body condition (BCS) from 2.5 to 3.5 (scale of 1 to 5), were not previously pregnant. The animals were allocated to 2 treatments: TEB treatment (n = 30) consisted of Day 0 insertion of progesterone intravaginal device (ID) plus 2 mg of estradiol benzoate (EB), i.m. followed on Day 8 by removal of the ID and 300 IU of eCG and 0.15 mg of PGF2α, i.m. on Day 9, 1 mg injection of EB (i.m.) was given, followed by FTAI at 48 to 56 h after the withdrawal of ID. The TEBGnRH12 treatment (n = 29) protocol was similar to TEB, but with administration of 25 μg of GnRH analogue (Lecirelina) 12 d after the FTAI. Transrectal ultrasound was used for pregnancy diagnosis on Day 35 after AI. Blood samples for P4 serum assay were collected from 30% of animals in each treatment, at the time of AI and on Days 5, 12, and 20 after FTAI. For all statistical analysis, we used the program SAS 9.0 (2002; SAS Institute Inc., Cary, NC, USA) at 5% probability. The pregnancy rate was analyzed by logistic regression. The effects of treatment and day in P4 concentration were analyzed in a split plot, with the effect of day in plot, in mixed model, considering the error and repetition as a random effect, and comparison of means by Tukey-Kramer. Pregnancy rate and the concentration of serum P4 on different days was analyzed by Spearman correlation. The pregnancy rate for TEB cows was 53.33% (16/30) for the first service compared with 37.93% (11/29) for TEBGnRH12 cows. The protocol used did not affect the pregnancy rate of crossbred cows (P > 0.05). There were no treatment differences (P > 0.05) between the concentrations of P4 (TEB = 3.88 ng mL-1; TEBGnRH12 = 3.12 ng mL-1). In conclusion, the administration of the analogue of GnRH 12 days after FTAI does not affect the rates of pregnancy or the concentration of P4. Supported by grants from CNPq, FAPEMIG and DZO-UFV.

The title compounds were prepared by arc-melting cold-pressed pellets of the elemental components. They crystallize with a tetragonal structure already reported for CeCr2Si2C. It was refined from single-crystal X-ray data of PrCr2S2C: P4/mmm, a - 402.2( 1) pm, c = 535.2(1) pm, Z = 1, R = 0.012 for 252 structure factors and 10 variable parameters. Magnetic susceptibility measurements with a SQUID magnetometer indicate Pauli paramagnetism for YCr2Si2C, while CeC2Si2C shows mixed valent behavior. The carbon atoms in the structure of these compounds are isolated from each other. The silicon atoms form pairs with a Si-Si distance of 245.3 pm, somewhat greater than the single-bond distance of 235.2 pm in elemental silicon. Together with the chromium atoms, the silicon pairs and carbon atoms form a three-dimensionally infinite polyanion, which has some similarity with the polyanions found in several related tetragonal structures, e.g., the structures of ThCr2Si2 and LuNi2B2C.

New intermetallic cadmium compounds RE2Rh2Cd (RE= La, Ce, Pr, Nd, Sm) were synthesized from the elements in sealed tantalum tubes in a high-frequency furnace. They were characterized through X-ray powder data: Mo2FeB2 type, space group P4/mbm, Z = 2. Single crystal data of the cerium compound (a = 762.8(1), c = 377.8(1) pm, wR2 = 0.0662, 199 F2 values, and 13 variable parameters) revealed small defects on the rhodium position leading to the composition Ce2Rh186(3)Cd for the investigated crystal. According to the course of the cell volumes Ce2Rh2Cd may be classified as a mixedvalent compound. The Ce2Rh2Cd structure is an intergrowth of slightly distorted AlB2 and CsCl related slabs of compositions CeRh2 and CeCd. Within the CeRh2 slab short Ce-Rh contacts (284-300 pm) are indicative of strong Ce-Rh bonding. The Rh-Rh distance within the AlB2 related slab is 289 pm.

Purpose In the Children's Oncology Group, risk group assignment for neuroblastoma is critical for therapeutic decisions, and patients are stratified by International Neuroblastoma Staging System stage, MYCN status, ploidy, Shimada histopathology, and diagnosis age. Age less than 365 days has been associated with favorable outcome, but recent studies suggest that older age cutoff may improve prognostic precision. Methods To identify the optimal age cutoff, we retrospectively analyzed data from the Pediatric Oncology Group biology study 9047 and Children's Cancer Group studies 321p1-p4, 3881, 3891, and B973 on 3,666 patients (1986 to 2001) with documented ages and follow-up data. Twenty-seven separate analyses, one for each different age cutoff (adjusting for MYCN and stage), tested age influence on outcome. The cutoff that maximized outcome difference between younger and older patients was selected. Results Thirty-seven percent of patients were younger than 365 days, and 64% were ≥ 365 days old (4-year event-free survival [EFS] rate ± SE: 83% ± 1% [n = 1,339] and 45% ± 1% [n = 2,327], respectively; P < .0001). Graphical analyses revealed the continuous nature of the prognostic contribution of age to outcome. The optimal 460-day cutoff we selected maximized the outcome difference between younger and older patients. Forty-three percent were younger than 460 days, and 57% were ≥ 460 days old (4-year EFS rate ± SE: 82% ± 1% [n = 1,589] and 42% ± 1% [n = 2,077], respectively; P < .0001). Using a 460-day cutoff (assuming stage 4, MYCN-amplified patients remain high-risk), 5% of patients (365 to 460 days: 4-year EFS 92% ± 3%; n = 135) fell into a lower risk group. Conclusion The prognostic contribution of age to outcome is continuous in nature. Within clinically relevant risk stratification, statistical support exists for an age cutoff of 460 days.

Two new species of Dorsiceratus Drzycimski, 1967 (Copepoda, Harpacticoida, Ancorabolidae), Dorsiceratus wilhelminae sp. nov. and D. dinah sp. nov. are described from Sedlo and Seine Seamounts, respectively (both northeast Atlantic). These are the first records of Dorsiceratus species from seamount summits. Both new species resemble the described species D. octocornis Drzycimski, 1967, D. triarticulatus Coull, 1973, and D. ursulae George, 2006, with respect to most morphological features. On the other hand, D. wilhelminae sp. nov. has long spinules at the inner margin of the A2 enp, while D. dinah sp. nov. bears two, rather than one, tubepores dorsally on third abdominal somite, and a geniculate first outer seta on P1 exp2. These characters are considered as apomorphic relative to the described Dorsiceratus species. As discussed in the present paper, the maintenance of a genus Dorsiceratus appears to be problematic. Although specimens may be assigned without difficulty to a group “Dorsiceratus”, such assignments are based on diagnostic features only; no clear-cut apomorphies have been detected so far to characterize the monophyly of Dorsiceratus. Just two apomorphic characters appear to be synapomorphies for all of the described Dorsiceratus species: 1) P2 enp2 with one rather than two setae and 2) P4 exp sexually dimorphic. Unfortunately, these features are relatively widespread within the Ceratonotus-group sensu Conroy-Dalton (2001) and therefore of rather low value. The authors decided, however, to retain the genus Dorsiceratus until new insights provide more information to support or disprove that hypothesis.

Abstract &lt;Background&gt;In the latest updated ASCO/CAP guideline, a new category, ER low-positive was introduced, which are determined by the 1% to10 % of positive staining of the tumor nuclei for ER. However clinical meaning of ER-low positive was unclear compared with ER- positive or ER-negative in HER2 negative breast cancer. &lt;Purpose&gt; In order to clarify the clinicopathological features of ER-low positive breast cancer, we compared the clinicopathological factors and prognosis among three groups, ER negative, ER-low positive, and ER-positive groups in the patients with HER2 negative breast cancer. &lt;Patients and Method&gt; A total of 1,882 patients with HER2 negative breast cancer who underwent surgery between 2001 and 2018 were included in this study. We divided them into three groups, ER negative (&lt;1%), ER-low positive (1-10%), and ER positive (10%≦). The relationships between ER status and clinicopathological characteristics and prognosis were evaluated. &lt;Result&gt;According to ER status, 553(29.4%), 183(9.7%), 1146(60.9%) patients were divided into ER negative, low-positive and positive groups. Compared with ER-positive group, patients in the ER negative and low-positive groups were of higher age (p&lt;.0001), and those tumors were significantly associated with the larger tumor size (p&lt;.0001), higher histological grade (p&lt;.0001) and more administration of adjuvant chemotherapy (p&lt;0.0001). Most of the patients with ER low-positive and ER-positive tumors had received the adjuvant endocrine therapy. The prognosis of the patients with ER low-positive tumors were poorer than that of those with ER positive tumors in terms of relapse-free survival (RFS p&lt;.0001), distant metastasis-free survival (DMFS p&lt;.0001) and overall survival (OS p&lt;.0001).In the node negative patients, the prognosis of the ER-negative and ER low-positive groups were equivalent, and poorer than that of the ER-positive group (RFS; p=0.0068, DMFS; p=0.0013, OS: p=0.0032). In addition, in pStage III patients, prognosis of the ER-negative and ER low-positive groups were also equivalent, and poorer than that of the ER-positive group (RFS; p=0.008, DMFS; p=0.0021, OS: p=0.0010). &lt;Conclusion&gt; This study showed that the prognosis of the patients with ER negative and ER low-positive were similar, and poorer than that of those with ER positive tumors. Therefore, the new category of ER-low positive is clinically especially important in order to determine the appropriate adjuvant therapy. Citation Format: Tajiri Wakako. The clinical importance of the new category, ER low-positive in the ER expression HER2 negative early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-05-11.