bluuebunny/crossref_metadata_2025 huggingface dataset:
Salmonella enterica Serotype Choleraesuis Infections in Pediatric Patients
Authors: Chiu Cheng-Hsun , Chuang Chih-Hsien , Chiu Shun , Su Lin-Hui , Lin Tzou-Yien
Published: May 2006

OBJECTIVE. Among >2500 nontyphoid Salmonella serotypes, Salmonella enterica serotype Choleraesuis shows a high predilection to cause systemic infections in humans. The objective of this study was to delineate the clinical and microbiologic features of pediatric patients with Salmonella Choleraesuis infections.

METHODS. Between May 1999 and February 2003, a total of 33 patients who were <18 years of age had culture-confirmed S Choleraesuis infections. Clinical features, laboratory values, treatment, outcome, and antimicrobial susceptibility patterns of the bacterial isolates were analyzed.

RESULTS. There were 24 males and 9 females with a mean age of 3 years. Fever (rectal temperature ≥38°C; 94%) was the most common clinical presentation. Sixteen (52%) had fever lasting >5 days before admission. Only 18 (54%) patients had diarrhea. The most common mode of infection is occult bacteremia without focal infection. Compared with data obtained from adult patients, the gastrointestinal manifestations appeared more frequently seen in pediatric patients. However, among the 18 who presented with diarrhea, 14 had concomitant bloodstream infection. Only 1 patient, who was a case of acute leukemia, died of S Choleraesuis sepsis. Resistance to ceftriaxone, ciprofloxacin, ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol was found in 6%, 28%, 88%, 76%, and 83% of the isolates, respectively.

CONCLUSION. Children with S Choleraesuis infections usually presented with occult bacteremia with mild gastrointestinal involvement. The mortality of S Choleraesuis infections in previously healthy children is low. Ciprofloxacin resistance among S Choleraesuis isolates from pediatric patients was lower than that of isolates from adult patients. In view of the high rate of multidrug resistance, third-generation cephalosporins seem to be the drug of choice for treatment of invasive S Choleraesuis infections.
Cardiac Involvement in Fukuyama-type Congenital Muscular Dystrophy
Authors: Nakanishi Toshio , Sakauchi Masako , Kaneda Yoshio , Tomimatsu Hirofumi , Saito Kayoko , Nakazawa Makoto , Osawa Makiko
Published: May 2006

BACKGROUND. Fukuyama-type congenital muscular dystrophy is an autosomal recessive disorder characterized by generalized skeletal muscle weakness and hypotonia from early infancy and by mental retardation. Little is known about cardiac involvement in patients with Fukuyama-type congenital muscular dystrophy. This study evaluated whether cardiac involvement exists in patients with Fukuyama-type congenital muscular dystrophy.

METHODS AND RESULTS. We evaluated left ventricular function using M-mode and Doppler echocardiography in 34 patients with Fukuyama-type congenital muscular dystrophy. The age ranged from 6 months to 30 years (median: 6 years). A total of 64 recordings were analyzed. Left ventricular dimensions and parameters of systolic function measured included left ventricular end-diastolic dimension, left ventricular fractional shortening, left ventricular wall thickness, and the mean velocity of circumferential fiber shortening and end-systolic wall stress relationship. Left ventricular end-diastolic dimension z score >2 was observed in 2 patients (6%). Left ventricular fractional shortening <0.28 and/or reduced mean velocity of circumferential fiber shortening in the mean velocity of circumferential fiber shortening-end-systolic wall stress relationship were observed in 16 patients (47%). A significant correlation between age and left ventricular fractional shortening was observed, and left ventricular fractional shortening decreased with age. Of 12 patients >15 years of age, 10 (83%) showed decreased left ventricular systolic function. Left ventricular fractional shortening was normal in most patients <10 years of age, and it was reduced in most patients >15 years of age. Five patients died of heart failure or respiratory problems, and a histologic examination confirmed the presence of myocardial fibrosis. No patients showed increased left ventricular wall thickness or a conduction abnormality on electrocardiograms.

CONCLUSION. Cardiac involvement exists in patients with Fukuyama-type congenital muscular dystrophy and becomes evident in older children in the second decade. A cardiac evaluation, including echocardiograms and subsequent follow-up, is important, especially in patients >10 years of age.
Mechanisms of Photoisomerization of Polyenes in Confined Media: From Organic Glasses to Protein Binding Cavities†
Authors: Liu Robert S. H. , Yang Lan‐Ying , Liu Jin
Published: May 2006

Photochemical reactivities of model organic systems (stilbene and diphenylbutadiene) in organic glasses were first examined and compared with those in solution and in organized media. These observations were in turn compared with reactivities of polyene chromophores in protein binding cavities (specifically PYP, rhodopsin and bacteriorhodopsin). The obvious conclusion is that the preference for the most volume‐conserving Hula‐twist mechanism isomerization in organic glasses is because of the close interaction between the guest and the host molecules. In organized media (zeolites, crystals and protein binding cavities), the residual empty space coupled with any specific guest–host interactions that are characteristic of a given system, could lead to involvement of the more volume‐demanding one‐bond‐flip (i.e.torsional relaxation) or bicycle‐pedal or an extended HT process in photoisomerization.
NF‐κB in Photodynamic Therapy: Discrepancies of a Master Regulator
Authors: Matroule Jean‐Yves , Volanti Cedric , Piette Jacques
Published: May 2006

Tumor eradication by photodynamic therapy (PDT) results from the onset of distinct killing processes. In addition to the well‐known necrotic and apoptotic mechanisms, PDT initiates an inflammatory response that will indirectly contribute to tumor clearance. The NF‐κB transcription factor is a major regulator of inflammation modulating the expression of cyto‐kines, chemokines, and adhesion molecules in various cell types in response to a large number of stimuli. Besides, NF‐κB regulates the expression of antiapoptotic genes, cyclooxygenases (COXs) and metalloproteinases (MMPs) as well, thereby favoring tumor cell proliferation and dissemination. In the present review, we aim to summarize the current knowledge on NF‐κB status following photosensitization of cancer cells and endothelial cells. In order to unravel the NF‐κB impact in PDT tumorigenicity and recurrences, we will stress the discrepancies of this major transcription factor relative to the signaling cascades underlying its activation and the cellular effects triggered by its translocation into the nucleus and its binding to its target genes.
Benign Breast Diseases: Classification, Diagnosis, and Management
Authors: Guray Merih , Sahin Aysegul A.
Published: May 2006

Learning Objectives

After completing this course, the reader will be able to: Discuss the clinical and histopathologic features of benign conditions of the breast.Identify the risks of benign lesions in relation to developing subsequent breast cancer.Describe the clinicopathologic features of benign neoplasms.

Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com

Benign breast diseases constitute a heterogeneous group of lesions including developmental abnormalities, inflammatory lesions, epithelial and stromal proliferations, and neoplasms. In this review, common benign lesions are summarized and their relationship to the development of subsequent breast cancer is emphasized.
Therapeutic Vaccines for Prostate Cancer
Authors: Tarassoff Christopher P. , Arlen Philip M. , Gulley James L.
Published: May 2006

Learning Objectives

After completing this course, the reader will be able to: List the different types of vaccines being studied clinically in prostate cancer.Explain the basic concepts of generating an active immune response.Discuss the clinical trials with prostate cancer vaccines including immunologic and clinical responses.

Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com

Prostate cancer is the most common, noncutaneous cancer for men in the U.S., leading to more than 30,000 deaths a year. Vaccines for prostate cancer, which for several years have been shown to generate immunologic responses, are beginning to show significant clinical promise. At present, numerous therapeutic options are being investigated, including autologous and allogeneic whole-tumor cell vaccines, dendritic cell vaccines, and poxvirus-based vaccines. Advances in basic immunology have translated into new, more complex therapeutic strategies. The findings from current trials and the demonstrated potential to combine vaccines with conventional therapies herald a promising future for the treatment of prostate cancer. This review highlights recent advances and clinical trials in immunotherapy for prostate cancer, along with current thoughts on immunologic and clinical monitoring of these trials.
Primary Mediastinal Large B-Cell Lymphoma
Authors: Savage Kerry J.
Published: May 2006

Learning Objectives

After completing this course, the reader will be able to: List the key clinical features of PMBCL.Discuss the literature on chemotherapy in PMBCL and the role of radiotherapy in PMBCL.Describe the pathologic features of PMBCL.

Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com

Primary mediastinal large B-cell lymphoma represents a distinct entity with unique clinicopathologic features and a molecular gene-expression signature reminiscent of nodular sclerosis subtype of classical Hodgkin's lymphoma. Recent studies, including those using a refined molecular signature, suggest that the outcome is more favorable than that of diffuse large B-cell lymphoma. Using historical comparisons, dose-dense and dose-intensive regimens may be more effective than cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy; however, the impact of adding rituximab to these regimens and effect on outcome comparisons is unknown. Clinical trials exploring these questions in addition to the benefit of consolidative radiotherapy are necessary to definitively answer these questions.
Intravascular Lymphoma: The Oncologist's “Great Imitator”
Authors: Zuckerman Dan , Seliem Rania , Hochberg Ephraim
Published: May 2006

Learning Objectives

After completing this course, the reader will be able to: Describe the clinicopathologic features of IVL that distinguish it from the other large-cell lymphomas.Discuss the diagnostic tests helpful in evaluating a case of suspected IVL.Explain the rationale for treatment approaches in patients with IVL, including the role of hematopoietic stem cell transplantation.

Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com

Intravascular lymphoma (IVL) is a rare subtype of extranodal diffuse large B-cell lymphoma with a distinct presentation. Anatomically the disease is characterized by the proliferation of clonal lymphocytes within small vessels with relative sparing of the surrounding tissue. The clinical symptoms of the disease are dependent on the specific organ involvement, which most often includes the central nervous system and skin. Because of the various modes of presentation and the rarity of IVL, the diagnosis is often made postmortem. The diagnosis is almost exclusively made by surgical biopsy of a suspected site of involvement. Advances in imaging and immunohistochemistry have led to increasing antemortem diagnosis of this lymphoma. Although some patients with this disease may be curable with aggressive therapy, further research into novel treatment strategies is needed to improve outcome. Some potential insights into future therapies may be drawn from the small amount of basic science literature relevant to this entity. This review provides a concise, up-to-date summary of IVL.
Ewing's Sarcoma Family of Tumors: Current Management
Authors: Bernstein Mark , Kovar Heinrich , Paulussen Michael , Randall R. Lor , Schuck Andreas , Teot Lisa A. , Juergensg Herbert
Published: May 2006

Learning Objectives

After completing this course, the reader will be able to: Describe the presentation, differential diagnosis, and prognosis for patients with Ewing's sarcoma.Explain the principles of multidisciplinary management of Ewing's sarcoma.Discuss the late effects of the therapy for Ewing's sarcoma.

Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com

Ewing's sarcoma is the second most frequent primary bone cancer, with approximately 225 new cases diagnosed each year in patients less than 20 years of age in North America. It is one of the pediatric small round blue cell tumors, characterized by strong membrane expression of CD99 in a chain-mail pattern and negativity for lymphoid (CD45), rhabdomyosarcoma (myogenin, desmin, actin) and neuroblastoma (neurofilament protein) markers. Pathognomonic translocations involving the ews gene on chromosome 22 and an ets-type gene, most commonly the fli1 gene on chromosome 11, are implicated in the great majority of cases. Clinical presentation is usually dominated by local bone pain and a mass. Imaging reveals a technetium pyrophosphate avid lesion that, on plain radiograph, is destructive, diaphyseal and classically causes layered periosteal calcification. Magnetic resonance best defines the extent of the lesion. Biopsy should be undertaken by an experienced orthopedic oncologist. Approximately three quarters of patients have initially localized disease. About two thirds survive disease-free. Management, preferably at a specialist center with a multi-disciplinary team, includes both local control—either surgery, radiation or a combination—and systemic chemotherapy. Chemotherapy includes cyclic combinations, incorporating vincristine, doxorubicin, cyclophosphamide, etoposide, ifosfamide and occasionally actinomycin D. Topotecan in combination with cyclophosphamide has shown preliminary activity. Patients with initially metastatic disease fare less well, with about one quarter surviving. Studies incorporating intensive therapy followed by stem cell infusion show no clear benefit. New approaches include anti-angiogenic therapy, particularly since vascular endothelial growth factor is an apparent downstream target of the ews-fli1 oncogene.
Prolactin inhibits cell loss and decreases matrix metalloproteinase expression in the involuting mouse mammary gland but fails to prevent cell loss in the mammary glands of mice expressing IGFBP-5 as a mammary transgene
Authors: Flint D J , Boutinaud M , Whitelaw C B A , Allan G J , Kolb A F
Published: May 2006

Insulin-like growth factor-binding protein 5 (IGFBP-5) mediates involution of the mammary gland. The decrease in DNA content and mammary gland weight which accompanies involution was inhibited by prolactin (PRL) in wild-type but not transgenic mice expressing IGFBP-5. Phospho-STAT5 protein levels were significantly lower in IGFBP-5 transgenic mice during lactation suggesting that IGFBP-5 antagonises PRL signalling in the mammary epithelium. In contrast, phospho-STAT3 levels increased during involution to a similar extent in both wild-type and transgenic mice and were unaffected by PRL. PRL inhibited gene expression of matrix metalloproteinases (MMPs) 3 and 12 but not tissue plasminogen activator or plasmin in wild-type and transgenic animals. The effects of PRL on MMPs appear to be indirect since PRL failed to inhibit MMP-3, -7 or -12 expression in HC-11 cells or in a co-transfection including an activated PRL receptor, STAT5 and a MMP-3-luciferase reporter gene. PRL is a potent inhibitor, both of cell death, an effect which is suppressed by IGFBP-5, and of MMP expression, which is independent of the actions of IGFBP-5.
Thyroid hormone-mediated negative transcriptional regulation of Necdin expression
Authors: Nygård Maria , Becker Nathalie , Demeneix Barbara , Pettersson Katarina , Bondesson Maria
Published: May 2006

Unliganded thyroid hormone receptors (apoTRs) repress transcription of hormone-activated genes by recruiting corepressors to the promoters. In contrast, on promoters containing so-called negative thyroid hormone response elements (nTREs), apoTRs activate transcription. A number of different molecular mechanisms have been described as to how apoTRs activate transcription varying with the target gene of the study. Here we demonstrate that thyroid hormone regulates the transcription of the Necdin gene, a developmentally regulated candidate gene for the genomic imprinting-associated neurobehavioural disorder, Prader–Willi syndrome. ApoTRs activate Necdin expression through an nTRE in its promoter, downstream of the transcription start site. The nTRE of the Necdin gene resembles the nTREs of the TSHβ genes of the hypothalamus–pituitary–thyroid axis in the sequence, position in the promoter, and mode of activation. We show that this group of nTRE-driven genes shares the requirements for binding of the retinoic X receptor and nuclear receptor corepressor/silencing mediator of retinoid and thyroid hormone receptors (NCoR/SMRT) for full ligand-independent activation, whereas there is no need for association of the p160 family of coactivators. In accordance with the requirement for corepressors, Necdin expression is influenced by deacetylase activity, suggesting that histone deacetylases and corepressors as well could function as activators of transcription, depending on the promoter context.
Defining high-fat-diet rat models: metabolic and molecular effects of different fat types
Authors: Buettner R , Parhofer K G , Woenckhaus M , Wrede C E , Kunz-Schughart L A , Schölmerich J , Bollheimer L C
Published: May 2006

High-fat (HF)-diet rodent models have contributed significantly to the analysis of the pathophysiology of the insulin resistance syndrome, but their phenotype varies distinctly between different studies. Here, we have systematically compared the metabolic and molecular effects of different HF with varying fatty acid compositions. Male Wistar rats were fed HF diets (42% energy; fat sources: HF-L – lard; HF-O – olive oil; HF-C – coconut fat; HF-F – fish oil). Weight, food intake, whole-body insulin tolerance and plasma parameters of glucose and lipid metabolism were measured during a 12-week diet course. Liver histologies and hepatic gene expression profiles, using Affymetrix GeneChips, were obtained. HF-L and HF-O fed rats showed the most pronounced obesity and insulin resistance; insulin sensitivity in HF-C and HF-F was close to normal. Plasma ω-3 polyunsaturated fatty acid (ω-3-PUFA) and saturated fatty acid (C12-C14, SFA) levels were elevated in HF-F and HF-C animals respectively. The liver histologies showed hepatic steatosis in HF-L, HF-O and HF-C without major inflammation. Hepatic SREBP1c-dependent genes were upregulated in these diets, whereas PPARα-dependent genes were predominantly upregulated in HF-F fed rats. We detected classical HF effects only in diets based on lard and olive oil (mainly long-chain, saturated (LC-SFA) and monounsaturated fatty acids (MUFA)). PUFA- or MC-SFA-rich diets did not induce insulin resistance. Diets based on LC-SFA and MUFA induced hepatic steatosis with SREBP1c activation. This points to an intact transcriptional hepatic insulin effect despite resistance to insulin’s metabolic actions.
Cell-specificity of transforming growth factor-β response is dictated by receptor bioavailability
Authors: Suszko Magdalena I , Woodruff Teresa K
Published: May 2006

Members of the transforming growth factor-β (TGFβ) family control diverse cellular responses including differentiation, proliferation, controlled cell death and migration. The response of a cell to an individual ligand is highly restricted yet the signaling pathways for TGFβ, activin and bone morphogenic proteins share a limited number of receptors and activate similar intracellular cytoplasmic co-regulators, Smads. A central question in the study of this family of ligands is how cells titrate and integrate each TGFβ-like signal in order to respond in a cell- and ligand-specific manner. This study uses the pituitary gonadotrope cell line, LβT2, as a model to delineate the relative contribution of TGFβ and activin ligands to follicle-stimulating hormone (FSH) biosynthesis. It was found that pituitary gonadotrope cells do not express the TGFβ type II (TβRII) receptor and are therefore not responsive to the TGFβ ligand. Transfection of the receptor restores TGFβ signaling capabilities and the TGFβ-mediated stimulation of FSHβ gene transcription in LβT2 cells. Consequently, we evaluated the presence of the TβRII in the adult mouse pituitary. TβRII does not co-localize with FSH-producing cells; however it is detected on the cell surface of prolactin- and growth hormone-positive cells. Taken together, these results suggest that the bioavailability of the TGFβ-specific receptor rather than TGFβ dictates pituitary gonadotrope selectivity to activin, which is necessary to maintain normal reproductive function. It is likely that the ligand-restricted mechanisms employed by the gonadotrope are present in other cells, which could explain the distinct control of many cellular processes by members of the TGFβ superfamily.
CCAAT/enhancer-binding protein δ activates the Runx2-mediated transcription of mouse osteocalcin II promoter
Authors: Shin Chan Soo , Jeon Min Jae , Yang Jae-Yeon , Her Sun-Ju , Kim Dohee , Kim Sang Wan , Kim Seong Yeon
Published: May 2006

CCAAT/enhancer-binding proteins (C/EBPs) are involved in the regulation of cell proliferation, differentiation, and control of metabolic function. Although the roles of C/EBPs in osteoblasts are largely unknown, both C/EBPβ and -δ have been shown to enhance rat osteocalcin promoter activity through the synergistic activation of Runx2 at the C/EBP element. Here we show that in the mouse, C/EBPδ increases the expression of osteocalcin whereas C/EBPβ does not. This increased expression was found to occur at the transcriptional level, as demonstrated by the increased transcriptional activity from mouse osteocalcin II (OG2) promoter by C/EBPδ. Although we found three putative C/EBP sites in the −637/±34 region of the OG2 promoter, none of these sites showed binding activity with in vitro translated C/EBP proteins. Notably, we show that C/EBPδ physically interacts with Runx2 and that C/EBPδ overexpression increases binding between the Runx2–C/EBPδ complex and the OSE2 element, a critical osteoblast-specific cis-acting element in the OG2 promoter. Consistent with these DNA binding data, a mutation in OSE2 abrogated the stimulatory effect of C/EBPδ on this promoter activity. Finally, chromatin immunoprecipitation analysis in MC3T3-E1 cells showed in vivo occupancy of the OG2 promoter by Runx2 and C/EBPδ. In conclusion, C/EBPδ was found to regulate mouse osteocalcin OG2 promoter activity indirectly by interacting with Runx2 in the context of the OSE2 element and this subsequently resulted in the cooperative activation of the OG2 promoter.
FOXL2 activates P450 aromatase gene transcription: towards a better characterization of the early steps of mammalian ovarian development
Authors: Pannetier Maëlle , Fabre Stéphane , Batista Frank , Kocer Ayhan , Renault Lauriane , Jolivet Geneviève , Mandon-Pépin Béatrice , Cotinot Corinne , Veitia Reiner , Pailhoux Eric
Published: May 2006

Previous studies have equated FOXL2 as a crucial actor in the ovarian differentiation process in different vertebrate species. Its transcriptional extinction in the polled intersex syndrome (PIS) leads primarily to a drastic decrease of aromatase (CYP19) expression in the first steps of goat ovarian development. In this study, we provide a better characterization of early ovarian development in goat, and we provide experimental evidence demonstrating that FOXL2 represents a direct transcriptional activator of the CYP19 gene through its ovarian-specific promoter 2. Moreover, the ovarian location of FOXL2 and CYP19 proteins, together with their expression profiles in the female gonads, stress the involvement of FOXL2 co-factor(s) for regulating CYP19 transcription. Expressional analyses show that activin-βA can be considered as a strong candidate for being one of these FOXL2 co-factors. Finally, we discuss evidence for a role of activin and estrogens in somatic and germinal cell proliferation occurring before germ cell meiosis. This period, of 20 days in goat, seems to have no equivalent in mouse. This species-specific difference could explain the phenotype discrepancy observed between XX goat PIS−/− and XX mouse Foxl2−/−.
GATA-4 is a granulosa cell factor employed in inhibin-α activation by the TGF-β pathway
Authors: Anttonen M , Parviainen H , Kyrönlahti A , Bielinska M , Wilson D B , Ritvos O , Heikinheimo M
Published: May 2006

Part of heterodimeric inhibin, inhibin-α is crucial for mammalian ovarian function. Regulation of inhibin-α expression in granulosa cells is both endocrine, primarily by follicle-stimulating hormone (FSH), and paracrine, primarily by members of the transforming growth factor β (TGF-β) superfamily. Smad proteins transmit TGF-β signals to the nucleus, but the cooperating transcription factors involved in inhibin-α promoter activation remain unknown. Transcription factor GATA-4 regulates inhibin-α in gonadal cells, and the FSH cascade activates GATA-4. We hypothesized that the TGF-β signalling cascade and GATA-4 also cooperate to regulate inhibin-α expression. In KK-1 granulosa tumour cells, which resemble normal granulosa cells and express inhibin-α, we found that TGF-β upregulated GATA-4 expression. Transient transfection experiments in KK-1 cells demonstrated that dominant negative GATA-4 variants or mutations of GATA-binding sites in the inhibin-α promoter attenuated TGF-β-induced gene activation. In GATA-4-deficient COS-7 cells, TGF-β enhanced the expression of the inhibin-α promoter only in the presence of exogenous GATA-4. Smad3, but not Smad2, cooperated with GATA-4 in the transcriptional activation of the inhibin-α promoter, and immunoprecipitation experiments in KK-1 cells revealed a physical Smad3:GATA-4 interaction. Our data suggest that GATA-4, interacting with Smad3, is a cofactor for TGF-β signalling to activate inhibin-α in granulosa cells.
FKBP12 functions as an adaptor of the Smad7–Smurf1 complex on activin type I receptor
Authors: Yamaguchi T , Kurisaki A , Yamakawa N , Minakuchi K , Sugino H
Published: May 2006

The cytoplasmic immunophilin FKBP12, a 12 kDa FK506-binding protein, has been shown to act as an inhibitor for transforming growth factor-β (TGF-β) signaling. FKBP12 binds to the glycine- and serine-rich motif (GS motif) of the TGF-β type I receptor, and functions as a secure switch to prevent the leaky signal. Upon stimulation with ligand, FKBP12 is released from the receptor to fully propagate the signal. We found that activin, a member of TGF-β superfamily, also induced the dissociation of FKBP12 from the activin type I receptor (ALK4). However, we observed that the released FKBP12 associates again with the receptor a few hours later. FKBP12 also interacted with another inhibitory molecule of activin signal, Smad7, in an activin-dependent manner, and formed a complex with Smad7 on the type I receptor. FK506, a chemical ligand for FKBP12, which dissociates FKBP12 from the receptor, decreased the interaction between Smad7 and Smad ubiquitin regulatory factor 1 (Smurf1). FK506 also inhibited the ubiquitination of the type I receptor by Smurf1. These findings indicate a new inhibitory function of FKBP12 as an adaptor molecule for the Smad7–Smurf1 complex to regulate the duration of the activin signal.
Antibody inhibition of synaptosomal protein of 25 kDa (SNAP-25) and syntaxin 1 reduces rapid exocytosis in insulin-secreting cells
Authors: Vikman Jenny , Ma Xiaosong , Hockerman Gregory H , Rorsman Patrik , Eliasson Lena
Published: May 2006

SNARE-proteins (soluble NSF-attachment protein receptor) are important for Ca2+-dependent exocytosis. We have used capacitance measurements and confocal imaging to dissect the role of synaptosomal protein of 25 kDa (SNAP-25) and syntaxin 1 in rapid exocytosis in insulin-secreting pancreatic β-cells. Following immunoneutralization of syntaxin 1 and SNAP-25, exocytosis was strongly reduced and associated with a marked reduction in the size of the readily releasable pool (RRP) by 65% and 86% in the presence of the anti-SNAP-25 and anti-syntaxin 1 antibodies respectively. The size of the immediately releasable pool (IRP), a subset of RRP in close association with the voltage-dependent Ca2+-channels, was reduced to an equal extent. The reduction in IRP correlated with slowed release kinetics and the time constant (τ) increased from a control value of 16 to 36 ms and 51 ms after inclusion of anti-SNAP-25 and anti-syntaxin 1 antibodies respectively in the pipette solution. We further show that SNAP-25 and syntaxin 1 aggregate in clusters along the plasma membrane. The size of these clusters was estimated to be ~300 nm and every β-cell contained ~400 SNAP-25/syntaxin 1 clusters. Whereas the inhibitory action of the anti-syntaxin 1 antibody on exocytosis could be attributed almost entirely to suppression of the voltage-dependent Ca2+-current (−40%), the effect of the anti-SNAP-25 antibody was not mediated by decreased Ca2+-entry and is more likely due to a direct interference with the exocytotic machinery. Our data are consistent with the concept that both syntaxin 1 and SNAP-25 are required for rapid exocytosis in β-cells.
Cortistatin mimics somatostatin by inducing a dual, dose-dependent stimulatory and inhibitory effect on growth hormone secretion in somatotropes
Authors: Luque R M , Peinado J R , Gracia-Navarro F , Broglio F , Ghigo E , Kineman R D , Malagón M M , Castaño J P
Published: May 2006

Cortistatin is a recently discovered neuropeptide that is structurally related to somatostatin, the classic inhibitor of growth hormone (GH) release. Cortistatin binds with high affinity to all five somatostatin receptors (sst1–5), and, like somatostatin, cortistatin inhibits in vivo GH release in man and rats. In this report, we compared the in vitro actions of cortistatin and somatostatin using primary pig pituitary cell cultures. In this species, we have previously reported that somatostatin not only inhibits GH-releasing hormone (GHRH)-stimulated GH release at high doses, but also stimulates basal GH release at low (pM) doses, a dual response that is markedly dependent on the subpopulation of pituitary somatotropes examined. Results reported herein demonstrate that cortistatin closely mimics the dose-dependent inhibitory and stimulatory effects of somatostatin on GH secretion. As cortistatin, unlike somatostatin, binds to the human receptor for ghrelin/GH secretagogs (GHS-R), we also investigated whether cortistatin stimulates GH release through this receptor by using a synthetic, short form of cortistatin, cortistatin-8 (CST8), which lacks the sst-binding capacity of full-length cortistatin but retains its GHS-R-binding capacity. Interestingly, CST8 stimulated GH release only at low doses (10−15 M), and did not reduce GH secretion stimulated by GHRH, ghrelin, or low-dose, full-length cortistatin, yet it counteracted that induced by a nonpeptidyl GHS, L-163 255. Taken together, our results indicate that the dual, inhibitory and stimulatory effects of cortistatin on GH release closely parallel those of somatostatin and are probably mediated by the same receptor(s) and signaling pathway(s) for both peptides. Furthermore, they suggest that the pathway(s) activated by cortistatin (and somatostatin) to stimulate GH release are not initiated by GHS-R activation.
Human chorionic gonadotropin-dependent induction of an equine aldo-keto reductase (AKR1C23) with 20α-hydroxysteroid dehydrogenase activity during follicular luteinization in vivo
Authors: Brown K A , Boerboom D , Bouchard N , Doré M , Lussier J G , Sirois J
Published: May 2006

Aldo–keto reductases (AKRs) are multifunctional enzymes capable of acting on a wide variety of substrates, including sex steroids. AKRs having 20α-hydroxysteroid dehydrogenase (20α-HSD) activity can reduce progesterone to 20α-hydroxy-4-pregnen-3-one (20α-DHP), a metabolite with lower affinity for the progesterone receptor. The objective of this study was to investigate the regulation of equine AKR1C23 during human chorionic gonadotropin (hCG)-induced ovulation/luteinization. The equine AKR1C23 cDNA was cloned and shown to encode a 322 amino acid protein that is conserved (71–81% identity) when compared with mammalian orthologs. RT-PCR/Southern blotting analyses were performed to study the regulation of AKR1C23 transcripts in equine preovulatory follicles isolated between 0 and 39 h after hCG treatment (ovulation occurring 39–42 h post-hCG). Results showed the presence of low AKR1C23 expression before hCG treatment, but a marked increase was observed in follicles obtained 12 h after hCG (P<0.05). Analyses of isolated preparations of granulosa and theca interna cells identified low mRNA expression in both cell types prior to hCG treatment, with granulosa cells clearly being the predominant site of follicular AKR1C23 mRNA induction. A specific polyclonal antibody was raised against a fragment of the equine protein and immunoblotting analyses showed an increase in AKR1C23 protein in granulosa cell extracts when comparing follicles isolated at 36 h post-hCG vs those collected prior to treatment, in keeping with mRNA results. Immunohistochemical data confirmed the induction of the enzyme in follicular cells after hCG treatment. The enzyme was tested for 20α-HSD activity and was shown to exhibit a KM of 3.12 μM, and a Vmax of 0.86 pmol/min per 10 μg protein towards progesterone. The levels of 20α-DHP measured in follicular fluid reflected this activity. Collectively, these results demonstrate for the first time that the gonadotropin-dependent induction of follicular luteinization is accompanied by an increase in AKR1C23 expression. Considering the 20α-HSD activity of AKR1C23, its regulated expression in luteinizing preovulatory follicles may provide a biochemical basis for the increase in ovarian 20α-DHP observed during gonadotropin-induced luteinization/ovulation. (The nucleotide sequence reported in this paper has been submitted to GenBank with accession number AY955082.)
Androgen receptor and prostate apoptosis response factor-4 target the c-FLIP gene to determine survival and apoptosis in the prostate gland
Authors: Gao Shen , Wang Hua , Lee Peng , Melamed Jonathan , Li Caihong X , Zhang Fahao , Wu Hong , Zhou Liran , Wang Zhengxin
Published: May 2006

Androgen receptor (AR) is a ligand-activated transcription factor that mediates the action of androgens and is essential for the growth, function, and cell differentiation of the prostate gland. Here, we demonstrated that the prostate apoptosis response factor-4 (par-4) functions as a novel AR coactivator. Par-4 physically interacted with the DNA-binding domain of AR, enhanced AR interaction with DNA, and increased AR-dependent transcription. Par-4 enhanced the c-FLIP promoter activity and was recruited on to the c-FLIP gene in the presence of androgens, and the dominant-negative par-4 decreased c-FLIP expression. These results suggest that, in addition to its proapoptotic function, par-4 acts as a novel transcription cofactor for AR to target c-FLIP gene expression. In addition, we demonstrated that loss of c-FLIP expression was essential for castration-induced apoptosis in the prostate gland and that enhanced c-FLIP expression was associated with prostate cancer progression to the androgen-resistant stage. Our data shed light on a transcription-mediated mechanism for the effects of the AR pathway on cell survival and apoptosis.
Vasopressin increases GAGA binding activity to the V1b receptor promoter through transactivation of the MAP kinase pathway
Authors: Volpi Simona , Liu Ying , Aguilera Greti
Published: May 2006

Previous studies show that binding of nuclear proteins to GAGA repeats (GAGA box) in the vasopressin type 1b receptor (V1bR) promoter is essential for transcriptional initiation of the gene. To determine whether increased vasopressin (VP) during stress activates V1bR expression through the GAGA box, we examined the effects of VP on GAGA binding activity and on the ability of the V1bR promoter to recruit RNA polymerase in the hypothalamic cell line, H32. In chromatin immunoprecipitation assays, VP induced RNA polymerase II recruitment by the wild type V1bR promoter but not by a construct with the major GAGA box deletion. VP (10 min) also increased binding of nuclear proteins to radiolabeled GAGA oligonucleotides in electromobility shift assays. VP-induced GAGA binding activity was potentiated by the protein kinase C inhibitor, calphostin C, and was prevented by the MEK inhibitor, UO126, and the epidermal growth factor receptor (EGFR) inhibitor, AG1478, suggesting that VP activates GAGA binding through transactivation of the EGFR. This was confirmed by western blot experiments showing rapid increases in phospho ERK after incubation with VP, an effect that was potentiated by calphostin C and inhibited by UO12 and AG1478, as well as by the ability of VP to phosphorylate the EGFR. Using receptor selective VP analogs we showed that both V1aR and V1bR subtypes can mediate GAGA binding activation in H32 cells. This study demonstrates that VP stimulates GAGA binding to the V1bR promoter through transactivation of the EGFR and MAP kinase. The data support the hypothesis that VP contributes to pituitary V1bR upregulation during stress through GAGA binding-mediated transcriptional activation.
Functional characterization and kinetic studies of an ancestral lamprey GnRH-III selective type II GnRH receptor from the sea lamprey, Petromyzon marinus
Authors: Silver M R , Sower S A
Published: May 2006

The recently cloned lamprey GnRH receptor was shown to have several unique features, including the longest intracellular C-terminal tail (120 amino acids (aa)) of any previously described GnRH receptor. In the current study, a series of experiments were performed examining cAMP responses, binding kinetics, whole cell competitive binding assays and internalization studies of the lamprey GnRH receptor using a series of three C-terminal tail truncations (80 aa, 40 aa and 0 aa) to better describe the functional significance of this unique vertebrate GnRH receptor. Activation of the lamprey GnRH receptor was shown to stimulate cAMP production in a dose-dependant manner when treated with either lamprey GnRH-I (LogEC50 −6.57±0.15) or lamprey GnRH-III (LogEC50 −8.29±0.09). Truncation analysis indicated that the membrane proximal 40 aa of the lamprey GnRH receptor C-terminal tail contain a motif required for cAMP accumulation. Saturation binding assays using the wild type and truncated lamprey GnRH receptors revealed that all of three truncated lamprey GnRH receptors were capable of binding lamprey GnRH-I. Competitive, intact cell-binding assays suggested that the lamprey GnRH receptor is lamprey GnRH-III selective, based on the observed pharmacological profile: lamprey GnRH-III (Inhibitory constant (Ki) 0.708±0.245 nM)=chicken GnRH-II (Ki 0.765±0.160 nM) > mammalian GnRH (Ki 12.9±1.96 nM) > dAla6Pro9NEt mammalian GnRH (Ki 21.6±9.68 nM) > lamprey GnRH-I (Ki 118.0±23.6). Finally, the lamprey GnRH receptor was shown to undergo rapid ligand-dependant internalization, which was significantly diminished in the tail-less truncated form. We have shown from our current and our previous structural studies that this unique lamprey GnRH receptor shares several characteristics of both type I and type II GnRH receptors which suggests that this receptor has retained ancestral characteristics that can provide insight into the function and evolution of the vertebrate GnRH receptor family.
Death or survival – progesterone-dependent cell fate decisions in the human endometrial stroma
Authors: Brosens J J , Gellersen B
Published: May 2006

The human endometrium undergoes cyclical waves of proliferation, differentiation and apoptosis in response to the rise and fall in ovarian oestradiol and progesterone levels. These hormonal responses in endometrial cells must be tightly kept in check to safeguard tissue homeostasis throughout reproductive life. The discovery that differentiating endometrium highly expresses the tumour suppressor p53, the forkhead transcription factor FOXO1, and promyelocytic leukaemia zinc finger protein (PLZF) has provided new insights into the molecular basis of life and death decisions in response to sex steroid hormones.
Techniques for Mammalian Cell Tissue Culture
Authors: Phelan Mary C.
Published: May 2006

This appendix opens with detailed discussions on the latest principles of sterile technique and preparation of culture media. Step‐by‐step protocols describe trypsinizing and subculturing monolayer cultures, passaging suspension cultures, freezing and thawing cells, counting cells using a hemacytometer, and preparing cells for transport.
Black Culture Centers: Still Central to Student Learning
Authors: Patton Lori D.
Published: May 2006

Are support and resource centers that serve students from single cultures still relevant after thirty years and in light of widespread interest in multiculturalism? Lori Patton argues that, at least in the case of black culture centers, these spaces continue to matter a great deal to students.
Hygrothermische Beanspruchung und Lebensdauer von Wärmedämm‐Verbundsystemen
Authors: Künzel Hartwig M. , Künzel Helmut , Sedlbauer Klaus
Published: May 2006

Das Alterungsverhalten und die Lebensdauer von Fassadensystemen wird stark von der hygrothermischen Beanspruchung beeinflußt. Neben den Witterungsbedingungen Temperatur, Strahlung und Luftfeuchte wirken häufig auch noch äußere oder innere Feuchtequellen, z. B. Schlagregen, Baufeuchte oder Oberflächenbetauung auf Außenwände ein. Wegen ihrer geringen Masse sind Wärmedämm‐Verbundsysteme (WDVS) davon z. T. besonders betroffen. Dennoch zeigt die Langzeitstudie an Objekten mit WDVS, daß damit keine erhöhte Schadensanfälligkeit verbunden ist. Abgesehen von einigen optischen Mängeln ist das Langzeitverhalten von WDVS als sehr positiv zu bewerten. Bei regelmäßiger Wartung entspricht die Lebensdauer von WDVS der von herkömmlich verputzten Außenwänden. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The Influence of Sawmill Wood Wastes on the Distribution and Population of Macroinvertebrates at Benin River, Niger Delta Area, Nigeria
Authors: Arimoro Francis O. , Osakwe Emeka I.
Published: May 2006

The impact of sawmill wood wastes on the distribution of benthic macroinvertebrates at the Sapele section of Benin River, Niger Delta, Nigeria, was investigated from March 2005 to August 2005. A total of 434 individuals were collected by kick‐sampling method, representing 21 taxa of benthic macroinvertebrates. Three stations, 1, 2, and 3, were selected from upstream of the site, receiving wood wastes discharge, the impacted site and its down stream, respectively. Among the water quality variables, conductivity, dissolved oxygen, biochemical oxigen demand (BOD5), nitrate‐nitrogen, phosphate‐phosphorus, transparency, and alkalinity were significantly different (P<0.05) among the stations. Orthogonal comparison by Duncan's multiple range test showed that station 2 (the impacted site) was the cause of the difference. More sensitive species such as Ephemeroptera or Plecoptera were completely absent from station 2, the impacted site. Species abundance was similar in station 1 and 3, indicating that the wood wastes must have adversely affected the distribution of these macroinvertebrates, especially the intolerant species. The wood waste discharge not only altered the water chemistry, but also stimulated the abundance of less‐sensitive macroinvertebrate species.
Ab Initio Molecular Dynamics Studies of Ionic Dissolution and Precipitation of Sodium Chloride and Silver Chloride in Water Clusters, NaCl(H2O)n and AgCl(H2O)n, n = 6, 10, and 14
Authors: Siu Chi‐Kit , Fox‐Beyer Brigitte S. , Beyer Martin K. , Bondybey Vladimir E.
Published: May 2006

An ab initio molecular dynamics method was used to compare the ionic dissolution of soluble sodium chloride (NaCl) in water clusters with the highly insoluble silver chloride (AgCl). The investigations focused on the solvation structures, dynamics, and energetics of the contact ion pair (CIP) and of the solvent‐separated ion pair (SSIP) in NaCl(H2O)n and AgCl(H2O)n with cluster sizes of n = 6, 10 and 14. We found that the minimum cluster size required to stabilize the SSIP configuration in NaCl(H2O)n is temperature‐dependent. For n = 6, both configurations are present as two distinct local minima on the free‐energy profile at 100 K, whereas SSIP is unstable at 300 K. Both configurations, separated by a low barrier (<10 kJ mol−1), are identifiable on the free energy profiles of NaCl(H2O)n for n = 10 and 14 at 300 K, with the Na+/Cl− pairs being internally solvated in the water cluster and the SSIP configuration being slightly higher in energy (<5 kJ mol−1). In agreement with the low bulk solubility of AgCl, no SSIP minimum is observed on the free‐energy profiles of finite AgCl(H2O)n clusters. The AgCl interaction is more covalent in nature, and is less affected by the water solvent. Unlike NaCl, AgCl is mainly solvated on the surface in finite water clusters, and ionic dissolution requires a significant reorganization of the solvent structure.
Low‐Temperature Phases of Rubidium Silver Iodide: Crystal Structures and Dynamics of the Mobile Silver Ions.
Authors: Funke Klaus , Banhatti Radha D. , Wilmer Dirk , Dinnebier Robert , Fitch Andrew , Jansen Martin
Published: May 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
New Type of Near‐Infrared to Visible Photon Upconversion in Tm2+‐Doped CsCaI3.
Authors: Beurer Eva , Grimm Judith , Gerner Pascal , Guedel Hans U.
Published: May 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis, Characterization, and Photocatalytic Properties of InVO4 Nanoparticles.
Authors: Zhang Liwu , Fu Hongbo , Zhang Chuan , Zhu Yongfa
Published: May 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Direct Asymmetric anti‐Mannich‐Type Reactions Catalyzed by a Designed Amino Acid.
Authors: Mitsumori Susumu , Zhang Haile , Cheong Paul Ha‐Yeon , Houk K. N. , Tanaka Fujie , Barbas Carlos F. III
Published: May 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
C—H Activation as a Strategic Reaction: Enantioselective Synthesis of 4‐Substituted Indoles.
Authors: Davies Huw M. L. , Manning James R.
Published: May 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Highly Diastereo‐ and Enantioselective Direct Aldol Reactions in Water.
Authors: Hayashi Yujiro , Sumiya Tatsunobu , Takahashi Junichi , Gotoh Hiroaki , Urushima Tatsuya , Shoji Mitsuru
Published: May 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Preparation of New, Optically Active 1,2‐Ferrocenyldiamine Ligands and Their Application to Ruthenium‐Catalyzed Asymmetric Transfer Hydrogenation of Ketones.
Authors: Fukuzawa Shin‐ichi , Suzuki Takashi
Published: May 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.