bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastric extremely well differentiated adenocarcinoma of gastric phenotype: as a gastric counterpart of adenoma malignum of the uterine cervix
Authors: Ae Lee Won 
Published: May 2005

Abstract

Background
Most of gastric adenocarcinoma can be simply diagnosed by microscopic examination of biopsy specimen. Rarely the structural and cellular atypia of tumor cells is too insignificant to discriminate from benign foveolar epithelium.

Case presentation
A 67-year-old male presented with a gastric mass incidentally found on the abdominal computed tomography (CT) for routine medical examination. Gastric endoscopic examination revealed a huge fungating mass at the cardia and mucosal biopsy was performed. Microscopically the biopsy specimen showed proliferation of bland looking foveolar epithelia in the inflammatory background and diagnosed as foveolar epithelial hyperplasia. Because the clinical and endoscopic features of this patient were strongly suggestive of malignancy, the patient underwent radical total gastrectomy. The resected stomach revealed a huge fungating tumor at the cardia. The cut surface of the tumor was whitish gelatinous. Microscopically the tumor was sharply demarcated from surrounding mucosa and composed of very well formed glandular structures without significant cellular atypia, which invaded into the whole layer of the gastric wall. Tumor glands were occasionally complicated or dilated, and glandular lumina were filled with abundant mucin. Immunohistochemically the tumor cells revealed no overexpression of p53 protein but high Ki-67 labeling index. The tumor cells and intraluminal mucin were diffusely expressed MUC1 and MUC5AC and only focally expressed MUC2. On abdominal CT taken after 12 months demonstrated peritoneal carcinomatosis and multiple metastatic foci in the lung.

Conclusion
The clinicopathologic profiles of gastric extremely well differentiated adenocarcinoma of gastric phenotype include cardiac location, fungating gross type, very similar histology to foveolar epithelial hyperplasia, foveolar mucin phenotype, lack of p53 overexpressoin and high proliferative index.
Dual effect of the SR proteins ASF/SF2, SC35 and 9G8 on HIV-1 RNA splicing and virion production
Authors: Jacquenet Sandrine , Decimo Didier , Muriaux Delphine , Darlix Jean-Luc 
Published: May 2005

Abstract
In HIV-1 infected cells transcription of the integrated provirus generates the single full length 9 kb viral RNA, a major fraction of which is spliced to produce the single-spliced 4 kb RNAs and the multiple-spliced 2 kb RNAs. These spliced RNAs are the messengers for the Env glycoproteins and the viral regulatory factors. The cellular SR and hnRNP proteins were shown in vitro to control alternative splicing by binding cis-regulatory elements on the viral RNA. To better understand in vivo the role of the SR proteins on HIV-1 genomic RNA splicing and virion production, we used a human cell line expressing high levels of complete HIV-1 and either one of the ASF/SF2, SC35, and 9G8 SR proteins. Results show that over-expressing SR proteins caused a large reduction of genomic RNA and that each SR protein modified the viral 9 kb RNA splicing pattern in a specific mode. In fact, ASF/SF2 increased the level of Vpr RNA while SC35 and 9G8 caused a large increase in Tat RNA. As expected, overexpressing SR proteins caused a strong reduction of total Gag made. However, we observed by immuno-confocal microscopy an accumulation of Gag at the plasma membrane and in intracellular compartments while there is a dramatic reduction of Env protein made in most cells. Due to the negative impact of the SR proteins on the levels of genomic RNA and HIV-1 structural proteins much less virions were produced which retained part of their infectivity. In conclusion, SR proteins can down-regulate the late steps of HIV-1 replication.
Prime–boost vaccination with plasmid and adenovirus gene vaccines control HER2/neu
+metastatic breast cancer in mice
Authors: Wang Xiaoyan , Wang Jian-Ping , Rao Xiao-Mei , Price Janet E , Zhou Heshan S , Lachman Lawrence B 
Published: May 2005

Abstract
Introduction
Once metastasis has occurred, the possibility of completely curing breast cancer is unlikely, particularly for the 30 to 40% of cancers overexpressing the gene for HER2/neu. A vaccine targeting p185, the protein product of the HER2/neu gene, could have therapeutic application by controlling the growth and metastasis of highly aggressive HER2/neu+ cells. The purpose of this study was to determine the effectiveness of two gene vaccines targeting HER2/neu in preventive and therapeutic tumor models.

Methods
The mouse breast cancer cell line A2L2, which expresses the gene for rat HER2/neu and hence p185, was injected into the mammary fat pad of mice as a model of solid tumor growth or was injected intravenously as a model of lung metastasis. SINCP-neu, a plasmid containing Sindbis virus genes and the gene for rat HER2/neu, and Adeno-neu, an E1,E2a-deleted adenovirus also containing the gene for rat HER2/neu, were tested as preventive and therapeutic vaccines.

Results
Vaccination with SINCP-neu or Adeno-neu before tumor challenge with A2L2 cells significantly inhibited the growth of the cells injected into the mammary fat or intravenously. Vaccination 2 days after tumor challenge with either vaccine was ineffective in both tumor models. However, therapeutic vaccination in a prime–boost protocol with SINCP-neu followed by Adeno-neu significantly prolonged the overall survival rate of mice injected intravenously with the tumor cells. Naive mice vaccinated using the same prime–boost protocol demonstrated a strong serum immunoglobulin G response and p185-specific cellular immunity, as shown by the results of ELISPOT (enzyme-linked immunospot) analysis for IFNγ.

Conclusion
We report herein that vaccination of mice with a plasmid gene vaccine and an adenovirus gene vaccine, each containing the gene for HER2/neu, prevented growth of a HER2/neu-expressing breast cancer cell line injected into the mammary fat pad or intravenously. Sequential administration of the vaccines in a prime–boost protocol was therapeutically effective when tumor cells were injected intravenously before the vaccination. The vaccines induced high levels of both cellular and humoral immunity as determined by in vitro assessment. These findings indicate that clinical evaluation of these vaccines, particularly when used sequentially in a prime–boost protocol, is justified.
Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in breast carcinoma in Jordan
Authors: Almasri Nidal M , Hamad Mohammad Al 
Published: May 2005

Abstract
Introduction
Although breast carcinoma (BC) is the most common malignancy affecting Jordanian females and the affected population in Jordan is younger than that in the West, no information is available on its biological characteristics. Our aims in this study are to evaluate the expression of estrogen receptor (ER) and progesterone receptor (PR) and Her-2/neu overexpression in BC in Jordan, and to compare the expression of these with other prognostic parameters for BC such as histological type, histological grade, tumor size, patients' age, and number of lymph node metastases.

Method
This is a retrospective study conducted in the Department of Pathology at Jordan University of Science and Technology. A confirmed 91 cases of BC diagnosed in the period 1995 to 1998 were reviewed and graded. We used immunohistochemistry to evaluate the expression of ER, PR, and Her-2. Immunohistochemical findings were correlated with age, tumor size, grade and axillary lymph node status.

Results
Her-2 was overexpressed in 24% of the cases. The mean age of Her-2 positive cases was 42 years as opposed to 53 years among Her-2 negative cases (p = 0.0001). Her-2 expression was inversely related to ER and PR expression. Her-2 positive tumors tended to be larger than Her-2 negative tumors with 35% overexpression among T3 tumors as opposed to 22% among T2 tumors (p = 0.13). Her-2 positive cases tended to have higher rates of axillary metastases, but this did not reach statistical significance. ER and PR positive cases were seen in older patients with smaller tumor sizes.

Conclusion
Her-2 overexpression was seen in 24% of BC affecting Jordanian females. Her-2 overexpression was associated with young age at presentation, larger tumor size, and was inversely related to ER and PR expression. One-fifth of the carcinomas were Her-2 positive and ER negative. This group appears to represent an aggressive form of BC presenting at a young age with large primary tumors and a high rate of four or more axillary lymph node metastases.
Differential responses to doxorubicin-induced phosphorylation and activation of Akt in human breast cancer cells
Authors: Li Xinqun , Lu Yang , Liang Ke , Liu Bolin , Fan Zhen 
Published: May 2005

Abstract
Introduction
We have shown previously that overexpression of constitutively active Akt or activation of Akt caused by constitutively active Ras or human epidermal growth factor receptor-2 (HER2) confers on breast cancer cells resistance to chemotherapy or radiotherapy. As an expanded study we here report differential responses in terms of phosphorylation and activation of Akt as a result of treatment with doxorubicin in a panel of breast cancer cell lines.

Methods
The levels of Akt phosphorylation and activity were measured by Western blot analysis with an anti-Ser473-phosphorylated Akt antibody and by in vitro Akt kinase assay using glycogen synthase kinase-3 as a substrate.

Results
Within 24 hours after exposure to doxorubicin, MCF7, MDA468 and T47D cells showed a drug-dose-dependent increase in the levels of phosphorylated Akt; in contrast, SKBR3 and MDA231 cells showed a decrease in the levels of phosphorylated Akt, and minimal or no changes were detected in MDA361, MDA157 and BT474 cells. The doxorubicin-induced Akt phosphorylation was correlated with increased kinase activity and was dependent on phosphoinositide 3-kinase (PI3-K). An increased baseline level of Akt was also found in MCF7 cells treated with ionizing radiation. The cellular responses to doxorubicin-induced Akt phosphorylation were potentiated after the expression of Akt upstream activators including HER2, HER3 and focal adhesion kinase.

Conclusion
Taken together with our recent published results showing that constitutive Akt mediates resistance to chemotherapy or radiotherapy, our present data suggest that the doxorubicin-induced phosphorylation and activation of Akt might reflect a cellular defensive mechanism of cancer cells to overcome doxorubicin-induced cytotoxic effects, which further supports the current efforts of targeting PI3-K/Akt for enhancing the therapeutic responses of breast cancer cells to chemotherapy and radiotherapy.
Renal blood flow in sepsis
Authors: Langenberg Christoph , Bellomo Rinaldo , May Clive , Wan Li , Egi Moritoki , Morgera Stanislao 
Published: May 2005

Abstract
Introduction
To assess changes in renal blood flow (RBF) in human and experimental sepsis, and to identify determinants of RBF.

Method
Using specific search terms we systematically interrogated two electronic reference libraries to identify experimental and human studies of sepsis and septic acute renal failure in which RBF was measured. In the retrieved studies, we assessed the influence of various factors on RBF during sepsis using statistical methods.

Results
We found no human studies in which RBF was measured with suitably accurate direct methods. Where it was measured in humans with sepsis, however, RBF was increased compared with normal. Of the 159 animal studies identified, 99 reported decreased RBF and 60 reported unchanged or increased RBF. The size of animal, technique of measurement, duration of measurement, method of induction of sepsis, and fluid administration had no effect on RBF. In contrast, on univariate analysis, state of consciousness of animals (P = 0.005), recovery after surgery (P < 0.001), haemodynamic pattern (hypodynamic or hyperdynamic state; P < 0.001) and cardiac output (P < 0.001) influenced RBF. However, multivariate analysis showed that only cardiac output remained an independent determinant of RBF (P < 0.001).

Conclusion
The impact of sepsis on RBF in humans is unknown. In experimental sepsis, RBF was reported to be decreased in two-thirds of studies (62 %) and unchanged or increased in one-third (38%). On univariate analysis, several factors not directly related to sepsis appear to influence RBF. However, multivariate analysis suggests that cardiac output has a dominant effect on RBF during sepsis, such that, in the presence of a decreased cardiac output, RBF is typically decreased, whereas in the presence of a preserved or increased cardiac output RBF is typically maintained or increased.
A quantitative analysis of the acidosis of cardiac arrest: a prospective observational study
Authors: Makino Jun , Uchino Shigehiko , Morimatsu Hiroshi , Bellomo Rinaldo 
Published: May 2005

Abstract
Introduction
Metabolic acidosis is common in patients with cardiac arrest and is conventionally considered to be essentially due to hyperlactatemia. However, hyperlactatemia alone fails to explain the cause of metabolic acidosis. Recently, the Stewart–Figge methodology has been found to be useful in explaining and quantifying acid–base changes in various clinical situations. This novel quantitative methodology might also provide useful insight into the factors responsible for the acidosis of cardiac arrest. We proposed that hyperlactatemia is not the sole cause of cardiac arrest acidosis and that other factors participate significantly in its development.

Methods
One hundred and five patients with out-of-hospital cardiac arrest and 28 patients with minor injuries (comparison group) who were admitted to the Emergency Department of a tertiary hospital in Tokyo were prospectively included in this study. Serum sodium, potassium, ionized calcium, magnesium, chloride, lactate, albumin, phosphate and blood gases were measured as soon as feasible upon arrival to the emergency department and were later analyzed using the Stewart–Figge methodology.

Results
Patients with cardiac arrest had a severe metabolic acidosis (standard base excess -19.1 versus -1.5; P < 0.0001) compared with the control patients. They were also hyperkalemic, hypochloremic, hyperlactatemic and hyperphosphatemic. Anion gap and strong ion gap were also higher in cardiac arrest patients. With the comparison group as a reference, lactate was found to be the strongest determinant of acidosis (-11.8 meq/l), followed by strong ion gap (-7.3 meq/l) and phosphate (-2.9 meq/l). This metabolic acidosis was attenuated by the alkalinizing effect of hypochloremia (+4.6 meq/l), hyperkalemia (+3.6 meq/l) and hypoalbuminemia (+3.5 meq/l).

Conclusion
The cause of metabolic acidosis in patients with out-of-hospital cardiac arrest is complex and is not due to hyperlactatemia alone. Furthermore, compensating changes occur spontaneously, attenuating its severity.
Randomized Phase III Trial of Cisplatin With or Without Topotecan in Carcinoma of the Uterine Cervix: A Gynecologic Oncology Group Study
Authors: Long Harry J. , Bundy Brian N. , Grendys Edward C. , Benda Jo Ann , McMeekin D. Scott , Sorosky Joel , Miller David S. , Eaton Lynne A. , Fiorica James V. 
Published: May 2005

Purpose On the basis of reported activity of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) or topotecan plus cisplatin in advanced cervix cancer, we undertook a randomized trial comparing these combinations versus cisplatin alone, to determine whether survival is improved with either combination compared with cisplatin alone, and to compare toxicities and quality of life (QOL) among the regimens. Patients and Methods Eligible patients were randomly allocated to receive cisplatin 50 mg/m2 every 3 weeks (CPT); cisplatin 50 mg/m2 day 1 plus topotecan 0.75 mg/m2 days 1 to 3 every 3 weeks (CT); or methotrexate 30 mg/m2 days 1, 15, and 22, vinblastine 3 mg/m2 days 2, 15, and 22, doxorubicin 30 mg/m2 day 2, and cisplatin 70 mg/m2 day 2 every 4 weeks (MVAC). Survival was the primary end point; response rate and progression-free survival (PFS) were secondary end points. QOL data are reported separately. Results The MVAC arm was closed by the Data Safety Monitoring Board after four treatment-related deaths occurred among 63 patients, and is not included in this analysis. Two hundred ninety-four patients enrolled onto the remaining regimens: 146 to CPT and 147 to CT. Grade 3 to 4 hematologic toxicity was more common with CT. Patients receiving CT had statistically superior outcomes to those receiving CPT, with median overall survival of 9.4 and 6.5 months (P = .017), median PFS of 4.6 and 2.9 months (P = .014), and response rates of 27% and 13%, respectively. Conclusion This is the first randomized phase III trial to demonstrate a survival advantage for combination chemotherapy over cisplatin alone in advanced cervix cancer.
Steroids and the Scientist
Authors: Gustafsson Jan-Åke 
Published: May 2005

AbstractOur interest in nuclear receptors (NRs) originated from early studies on hepatic steroid metabolism. We discovered a new hypothalamo-pituitary-liver axis, imprinted neonatally by androgens and operating through sexually differentiated GH secretory patterns. Male and female patterns have opposite effects on sexually differentiated hepatic genes, explaining sexually dimorphic liver patterns. To further understand steroid action, we purified the glucocorticoid receptor (GR) leading to our discovery of the NR three-domain structure, with separable DNA binding domain and ligand binding domains and a third domain now known to have transcriptional regulatory properties. Knowledge of this domain structure has been immensely important for deciphering NR actions. Using this first purified NR, we collaborated with Keith Yamamoto and first demonstrated specific NR binding to DNA. This also was the first demonstration of a mammalian transcription factor, a breakthrough that led to discovery of NR response elements. In further collaboration with Yamamoto, we cloned the first NR cDNA sequences, leading to cloning of the superfamily of NR genes. With Yamamoto and Kaptein, we determined the first three-dimensional NR structure, that of DNA binding domain. Later work on orphan receptors resulted in the first discovery of: 1) endogenous ligands for an orphan receptor (fatty acids as activators of peroxisomal proliferator-activated receptor α); 2) liver X receptor β (OR-1) and its role in central nervous system cholesterol homeostasis; and 3) estrogen receptor β, leading to a paradigm shift in understanding of estrogen signaling, of importance in endocrinology, immunology, and oncology and to development of estrogen receptor β agonists for treatment of autoimmune diseases, prostate disease, depression, and ovulatory dysfunction.
The Contribution of “Alternative Approaches” to Understanding Steroid Hormone Action
Authors: Jensen Elwood V. 
Published: May 2005

Abstract
In the 47 yr since the first evidence for a steroid hormone receptor was presented at an international congress to an audience of five persons, the concept of “alternative approach” has played an important role in providing new understanding. By asking not what does an estrogenic hormone do to cellular processes in responsive tissues but what do these cells do to the hormone, it was shown that rat uterus contains a characteristic protein with which the hormone associates to promote growth. In the following decade, it was established that this substance is a true receptor, involved in hormonal action. Furthermore, estradiol was found not to undergo a chemical change as it exerts its effect. Finally, estrogenic action was established as a two-step process in which association with the hormone converts the receptor from an inactive to an active form that can bind tightly in the nucleus to modify transcription. These findings, obtained by studying the fate of the hormone itself, disproved the then accepted concept that estrogens interact with enzyme systems, and opened a new field of research. Soon various laboratories identified intracellular receptors for all classes of steroid hormones, the action of which involves a similar two-step process. Several laboratories then attempted, without success, to obtain antibodies to these receptors by conventional techniques. The unconventional approach of gradient ultracentrifugation, using radioactive estradiol as a marker for the receptor, gave a means of recognizing the soluble immune complexes formed with estrogen receptor and provided the first antibodies to any steroid hormone receptor, permitting its cloning. Finally, the knowledge that estrogens act through a receptor suggested that measuring the receptor content of an excised tumor specimen could identify, in advance, two thirds of the human breast cancers that are not estrogen dependent. These patients will not benefit from endocrine ablation or antiestrogen treatment and should be placed directly on chemotherapy. This is now standard clinical practice.
SymbioticHydraexpress a plant-like peroxidase gene during oogenesis
Authors: Habetha Matthias , Bosch Thomas C. G. 
Published: May 2005

SUMMARYSymbiotic associations accompanied by gene exchange between the symbionts form the phylogenetic origin of eukaryotic cells and, therefore, had significant impact on species diversity and evolutionary novelty. Among the phylogenetically oldest metazoan animals known to form symbiotic relationships are the Cnidaria. In the Cnidarian Hydra viridis, symbiotic algae of the genus Chlorella are located in endodermal epithelial cells and impact sexual differentiation. When screening for Hydra viridis genes that are differentially expressed during symbiosis, we found a gene, HvAPX1, coding for a plant-related ascorbate peroxidase. HvAPX1 is expressed exclusively during oogenesis and in contrast to all known ascorbate peroxidase genes in plants does not contain introns. No member of this gene family has previously been identified from a member of the animal kingdom. We discuss the origin of the HvAPX1 gene and propose that it may have been transferred horizontally following an endosymbiotic event early in evolution of the Hydra lineage as an RNA or cDNA intermediate.
Learning in two contexts: the effects of interference and body size in bumblebees
Authors: Worden Bradley D. , Skemp Ana K. , Papaj Daniel R. 
Published: May 2005

SUMMARY
We examined the effect of learning a new task on the performance of a previously learned task with the same set of visual cues in bumblebees, Bombus impatiens. Previous studies have shown that given a binary choice at each task, bumblebees do not show retroactive interference, or mistakes in the first task, if the two tasks are in different contexts,feeding and nest location. Here we tested whether adding a third, unrewarded choice to each task affects the performance of bees learning in two contexts. In addition, we examined whether workers differ in their expression of interference and learning ability based on size. Performance of workers at a feeder task was degraded by the introduction of training to a second task at the nest entrance. Mistakes at the feeder were biased toward the color cue that was not rewarding in both tasks; suggesting that irrelevant or background stimuli are more prone to decay or forgetting during interference. With respect to interference, we did not find an effect of body size on the amount of interference; however, size was related to how quickly interference occurred. Among individuals showing retroactive interference, larger bees showed interference earlier in phase 2 than did smaller bees. Overall, larger workers learned each task more rapidly than smaller workers. We conclude that the timing of interference is a tradeoff between acquisition of the new task and performance at a previously learned task. Given that foragers in nature tend to be larger than nest workers, we suggest that size-related learning differences be considered as a factor in division of labor between large and small bumblebees.