bluuebunny/crossref_metadata_2025 huggingface dataset:
Composting of Solid Waste During Extended Human Travel and Habitation in Space
Authors: Hogan J.A. , Finstein M.S.
Published: October 2007

As part of a Controlled Ecological Life Support System (CELSS) for long term human travel and habitation in space, the resources in solid waste may be regenerated through the microbiological process of composting. This would release CO2 for photosynthetic uptake while transforming the waste to a smaller volume and weight of stabilized and sanitized compost. To continue the biodegradation and complete the cycling of nutrients, the compost would be incorporated into soil used in growing food crops. To minimize the weight and volume of the composting facility, the rate of the transformation should be maximized. This is realizable through ventilative removal of heat in reference to a biologically favorable temperature ceiling, and maintenance of a thoroughly oxygenated state. A preliminary design for a composting system for use in a spacecraft and/or permanent space station is proposed.
Assessment of the Potential Health Risks Associated With the Dissemination of Micro-Organisms From a Landfill Site
Authors: Fedorak Phillip M. , Rogers Robert E.
Published: October 2007

In planning for a new sanitary landfill site, the City of Edmonton, Canada considered the potential for dissemination of micro-organisms via aerosols and by gulls that feed on the refuse. The health impacts on the residents and chicken and mushroom farming activities in the vicinity of the proposed location were assessed. Conclusions based on a review of information in the literature and in the City's planning documents were: (1) the densities of airborne microbes generated at the landfill site would be less than those observed at sewage treatment plants which cause very little health risk; (2) chicken and mushroom farming operations generate very high densities of airborne microbes and the small numbers of microbes that might originate from the landfill site would be insignificant; (3) the proximity of the proposed landfill location to an existing landfill site would not likely change the number of gulls in the area; (4) sound agricultural practices (such as preventing wild birds from contacting poultry, or their water supplies, food and new litter) will minimize risk of the spread of pathogens to chickens from gulls.
Phagocytosis of Bioactive Microspheres
Authors: Ikada Y. , Tabata Y.
Published: October 2007

The influence of several proteins on the uptake of microspheres was investigated using mouse peritoneal macrophages. Thioglycollate-stimulated macrophages were cultivated for 3 h with protein-grafted and protein-coated cellulose microspheres smaller than 2 μm in the presence and the absence of serum. Bovine serum albumin reduced the phagocytosis of microspheres, while y-globulin, human fibronectin, bovine tuftsin, and gelatin enhanced the phagocytosis. This trend was not influenced substantially by the presence of serum and the mode of surface binding of the proteins; that is, covalent grafting or physical adsorption (coating). However, in the case of gelatin binding, phagocytosis was greatly enhanced by the presence of serum as compared with the other proteins.
Opportunities for Progressive Pharmacy Practice in Homecare
Authors: Klotz Roger
Published: October 2007

This article will describe the many opportunities for progressive pharmacy practice in the homecare area, particularly when dealing with parenteral therapies. Progressive pharmacy practice in the home requires that the technical and clinical pharmacy expertise first developed in the institutional setting be applied in a decentralized environment. The decentralization of high-tech care into the patient's home presents major challenges and opportunities to all health care professionals. The pharmacist, in particular, is given the opportunity to provide progressive pharmacy services, especially clinical services, as a result of patient need and agency requirements (ie, JCAHO, State Pharmacy Board, HCFA). This group of patients has generally a higher acuity than traditional ambulatory and homecare patients; thus, health care professionals, reimbursement organizations, and regulatory and accrediting agencies are very concerned about the coordination of patient care. The pharmacist's knowledge base and interest in drug therapy is well suited for and used to benefit the patient and health-care team; this is important in many areas of patient care. A knowledge of drug therapies is required in predischarge planning, patient training, plan of care development, and patient monitoring. Therefore, the hospital and/or homecare pharmacist can be involved from the start (patient selection) to the completion of therapy for the homecare patient. Since homecare patients have an increasing acuity, the traditional hospital pharmacy services need to be provided and expanded upon so that safe and efficacious therapy is provided.
High-Technology Home Pharmacotherapy, II: An Overview of the Newest Home Therapies
Authors: Bennett Mary A. , Allen Ronald D.
Published: October 2007

This article provides an overview of a group of therapies previously considered as exclusively inpatient treatments. Cardiovascular therapies have moved out of the intensive care unit and into the outpatient setting. Parenteral anticoagulation is also handled at home, using aggressive patient selection and monitoring criteria. Premature labor management, once requiring lengthy hospitalization, is another treatment transplanted from the inpatient setting. The ongoing research in immune modifier therapy has produced agents, both approved and investigational, that have found a place in home care. Several other parenteral therapies now performed routinely outside of the hospital include hematologic agents, blood, hormones, and steroids. Rapid growth in these home settings affords the pharmacist fertile ground for challenging clinical practice.
Considerations in the Treatment of Acquired Immunodeficiency Syndrome Patients at Home
Authors: Matsumoto Sandra A. , Seideman Mary Frances
Published: October 2007

The rapidly growing acquired immunodeficiency syndrome (AIDS) population faces frequent, expensive hospitalization due to the debilitating sequelae of the disease. Home care offers these patients an opportunity to receive or complete their therapy in comfortable surroundings, allowing them to realize the psychosocial and financial benefits of outpatient care. A myriad of sophisticated drug therapies has been successfully administered in the home setting. Therapy for frequently occurring opportunistic infections often requires treatment with highly toxic drugs such as amphotericin, pentamidine, and ganciclovir. With thorough patient training and diligent monitoring by the home-care pharmacist and nurse, these agents can be safely administered at home. Conventional and investigational chemotherapy and immunomodulator therapy, such as interferon or erythropoeitin, can also be administered at home. Providing total parenteral nutrition to AIDS patients is a controversial treatment modality, but if indicated, it can also be accomplished at home. Outpatient pain management has allowed many patients with terminal or chronic illnesses to minimize time spent in hospitals or extended care facilities, and it can offer the same advantages to patients with AIDS. The psychosocial ramifications of AIDS and its impact on patients and health care professionals must be understood in order to effectively provide total patient care at home. The challenge to the homecare pharmacist is to acquire and maintain a comprehensive knowledge of the treatment options currently available for the management of AIDS.
Pharmacy-The Last Contact in the Recovery Process: A Discharge Medication Service
Authors: Simmons Glenn E. , Dorsey Ann B. , Nosek Ronald A. , Vranjican Mladen , Jelks Daniel F. , Godbout N.P. , Lane C.B.
Published: October 2007

Patient compliance is an essential element in the recovery process whether it is postsurgical care or disease management. It has been shown that the more knowledgeable a patient is about his therapy, the more likely he is to be compliant with that therapy. The Pharmacy Department at Portsmouth Naval Hospital undertook a program to try to increase the patients' knowledge of their drug regimens and enhance their perception of pharmacy's role in health care. In today's age of consumerism, both of these were considered desirable goals. This was accomplished by establishing a service whereby the pharmacy picked up prescriptions from the nursing unit and filled them in the outpatient pharmacy prior to the patient's arrival at the pharmacy. The medications were discussed with the patient in a quiet setting, prior to their leaving the hospital. This is a US government work. There are no restrictions of its use.
Transition of Products From Prescription to Over the Counter: The H2 Antagonists
Authors: Drea Edward J.
Published: October 2007

In general, the histamine type-2 receptor antagonists (H2RA) enjoy an enviable record of safety. These agents, notably cimetidine, have been studied extensively in clinical trials, case reports, and worldwide drug use reporting systems. Of the available agents (cimetidine, famotidine, nizatidine, and ranitidine) several similarities exist from compound to compound and use data to support that each of the agents is equally safe and efficacious in equipotent dosing. A review of H2RA pharmacology, pharmacokinetics, adverse effects, and drug interactions is included to provide the clinician with a basis for rational selection and use of an H2RA.
Pharmacists' Practice in Managed Health Care
Authors: Barenbaum Larry
Published: October 2007

The saga of managed care pharmacy and its impact on pharmacy practice patterns is still ongoing, even with renewed vigor. There is significant recognition in the marketplace for the development of a managed care pharmacy specialty. Growth of a divergent practice pattern can be somewhat stilted because currently there is not a formal training ground or any other resource. Presented herein is just one path to acquiring experience.
Therapeutic Issues in the Evaluation and Treatment of the Hypertensive Patient: White Coat Hypertension and Once Daily Dosing of Antihypertensive Agents
Authors: Wilson Marcus D.
Published: October 2007

Pharmacists are an invaluable resource of drug and other treatment information for the primary provider because of their skills in drug literature evaluation and retrieval. The implementation of a home blood pressure monitoring program at the HMO of Delaware has allowed the establishment of excellent relations between medical, nursing, and pharmacy personnel and has allowed the pharmacist to become involved in the decision-making process for many hypertensive patients.
Playing power: gendered discourses in a computer games magazine
Authors: Thornborrow Joanna
Published: October 2007

The focus of this article is the language of computer game previews and guides in the magazine Sega Mean Machines. I examine the presence of conflicting discourses within these texts, and discuss the possible effects they may have on the construction of gender-specific identities for the reader. Through a stylistic analysis of these texts, I will argue that entering the computer game-playing world means essentially a shift for the female readers/players into male-centred discourses.
The Effects of Group Therapy on Siblings of Pediatric Oncology Patients
Authors: Heiney Sue P. , Goon-Johnson Karen , Ettinger Robert S. , Ettinger Sandra
Published: October 2007

The stress and psychological difficulties of siblings of children with cancer is well documented. Siblings must cope with a myriad of emotions, isolation from the family, and many changes in daily life. Therefore, a need exists to determine the effects of psychosocial interventions on siblings of cancer patients. The support group is one psychosocial intervention that has been suggested as a method to relieve stress and enhance coping. A quasi-experimental design was selected to determine the effects of participation in a support group on the social adjustment of siblings of children with cancer. Conclusions suggest that a support group provides siblings with the opportunity to decrease their sense of isolation, ventilate negative feelings, and learn from each other. Additionally, descriptive data suggest a need for ongoing follow-up with siblings to help them manage the stresses emerging from the impact of the diagnosis and treatment on the family. Implications of this study suggest that nurses should organize support groups for siblings and/or refer them to existing groups. Also, this study suggests the need to work with siblings and educate parents regarding sibling concerns.
Diabetes Insipidus and Syndrome of Inappropriate Secretion of Antidiuretic Hormone in Children with Midline Suprasellar Brain Tumors
Authors: Shiminski-Maher Tania
Published: October 2007

Salt and water balance within the body is controlled by the hormonal influence of vasopressin. Vasopressin is produced in the hypothalamus, stored and released from the posterior lobe of the pituitary, and travels via the blood to the kidneys to regulate the amount and concentration of urine excreted. Oversecretion or undersecretion of vasopressin, eg, diabetes insipidus (DI) or syndrome of inappropriate secretion of antidiuretic hormone (SIADH) results in an imbalance of the salt-to-water ratio. In children this hormonal imbalance may occur secondary to a suprasellar brain tumor and/or the treatment of such. Approximately 50% to 75% of children with suprasellar tumors will develop permanent DI and the remainder will experience transient postoperative DI or SIADH. Pathophysiology of vasopressin's control on salt and water balance and its relationship to suprasellar brain tumors in children are presented. Nursing assessment and intervention parameters for management of DI and SIADH in children with brain tumors are also discussed.
The Effects of Group Therapy on Bereaved Extended Family of Children With Cancer
Authors: Heiney Sue P. , Wells Linda M. , Gunn Jim
Published: October 2007

The impact of the death of a child from cancer and subsequent grief on the extended family members has not been documented. Additionally, the effect of a support group for these individuals has not been explored. Therefore, this one group pretest/post-test study sought to determine the effects of participation in a support group for bereaved extended family members whose child died from cancer. Extended family members completed the Emotions Profile Index before and after the group sessions. Descriptive data were collected from the cotherapists' process log and the participants' evaluation. No significant differences were found between pretest and post-test scores for any emotional state. However, the group process log showed significant clinical data related to the intensity of the grief experienced and ways of coping with the loss. The Bereaved Extended Family Group Evaluation demonstrated the usefulness of the group experience. Tentative conclusions support the value of such a group in providing a forum for the bereaved extended family to ventilate feelings of anger and sadness and find ways to cope with the future.
What Caused My Child's Cancer? Parents' Responses to an Epidemiology Study of Childhood Cancer
Authors: Ruccione Kathleen S. , Waskerwitz Mary , Buckley Jonathan , Perin Gail , Hammond G. Denman
Published: October 2007

When a child is diagnosed with cancer, parents try to understand why the cancer developed. Although usually it is not possible to explain what caused an individual child's cancer, clinical experience has shown that parents do form theories about the origins of their child's illness although, or perhaps because, no one knows the actual cause. A parent-completed epidemiology questionnaire (EQ), designed to provide a comprehensive and general epidemiology data base for studies conducted by the Childrens Cancer Group, included an open-ended item ("Do you have any additional comments or concerns about anything that could have caused or contributed to your child's illness?"). A convenience sample of 500 EQs containing responses to the open-ended question was reviewed independently by two experienced pediatric oncology nurses. Statements contained in the responses were categorized into 12 major themes according to content: concern about environmental exposures (n = 303), concern about family health history (n = 270), specific causality attribution (n = 39), puzzlement (n = 24), concern with cancer "clusters" (n = 23), concern with stress (n = 22), altruism (n = 15), specific feedback requests (n = 11), myths/misconceptions (n = 5), advocation of preventive education/screening (n = 4), active information-seeking (n = 6), and parental self-blame (n = 4). These themes or concerns provide useful information that can be applied in planning educational and supportive clinical interventions, as well as further research.
Parental Concerns Following a Child's Discharge From a Bone Marrow Transplant Unit
Authors: White Andrea M.
Published: October 2007

The purpose of this descriptive study was to explore the concerns of parents following a child's discharge from a bone marrow transplant unit. A qualitative approach which included components of grounded theory was used to explore the posttransplant experience from the parents' perspective. Seven parents of five children who were transplanted for a variety of malignancies at a number of out-of-state centers were intenviewed about their experiences. Chart analysis and participant observation provided additional sources of data. Initial coding of audio-taped interviews revealed 32 topics of concern voiced by the parents. Use of the constant comparative analysis technique resulted in the emergence of six major themes of the posttransplant experience. The Return Home, Changing Relationships, Working with This, Learning the Rules, The New Norm, and The Uncertain Future were components of this transitional period for each family. Similarities were found between the experiences of study parents and the parents of chronically ill children and parents or spouses of organ transplant recipients. Awareness of posttransplant concerns may facilitate the efforts of both transplant and referral center staff to educate, support, and care for these children and their families.
Smoking Prevention in Childhood Cancer Survivors
Authors: Bolinger Carol
Published: October 2007

In the year 2000, there may be 220,000 adult survivors of childhood cancer. This creates new emphasis on the health of long-term survivors. The oncology team is responsible for educating patients about methods of modifiable risk reduction for the development of cancer. Smoking is the single most avoidable risk factor implicated in the development of cancer, yet survivors of childhood cancer have been found to smoke at the same rate as their peers. Nurses play a key role in developing patients' knowledge, beliefs and skills to avoid smoking behaviors.
Comparison of Axillary and Infrared Tympanic Membrane Thermometry in a Pediatric Oncology Outpatient Setting
Authors: Androkites Arlene L. , Werger Annette M. , Young Mary L.
Published: October 2007

The purpose of this study was to determine whether infrared tympanic membrane thermometry can replace mercury-in-glass temperatures as an assessment tool for detecting fevers earlier and more reliably in a pediatric oncology outpatient setting. A total of 313 patient visits had infrared tympanic temperatures (obtained by using the LighTouch LTX Pedi-Q thermometer (Exergen; Watertown, MA) and axillary temperatures taken simultaneously (obtained by using mercury-in-glass thermometers). Those patients with a normal axillary temperature and an elevated tympanic measurement of 38°C or higher had a follow-up axillary temperature conducted that evening to determine whether an elevated tympanic temperature predicted on coming fever or infection. The mean tympanic temperature was 37.5°C and the mean axillary temperature was 36.8°C, a difference of 0.7°C (P = .0001). Sixty-two (20%) patients had discrepant temperatures with a febrile tympanic and normal axillary measurement. Three (5%) of these patients were febrile at their follow-up axillary reading. Tympanic thermometry resulted in a signigcantly higher temperature reading than the axillary method. Elevated tympanic temperatures were not predictive of oncoming fever or infection. Fevers were not missed when using the tympanic method. To prevent unnecessary medical intervention, it is recommended that mercury-in-glass thermometers verify elevated tympanic temperatures.
The Role of the Pediatric Nurse Practitioner in the Comprehensive Management of Pediatric Oncology Patients in the Inpatient Setting
Authors: Christensen Joy , Akcasu Nur
Published: October 2007

The role of the pediatric nurse practitioner (PNP) in the comprehensive management of pediatric oncology patients in the inpatient setting was examined at a large tertiary teaching hospital. This article shows role responsibilities including new diagnosis teaching, procedures, routine chemotherapy, patients' comprehensive medical management, coordination of nursing care across settings, phone triage, and professional development. A PNP's typical day is highlighted to illustrate the innovative merging of traditional ambulatory care roles with that of the PNP as a comprehensive manager of pediatric oncology patients in the inpatient setting. This role provides a more seamless care experience and provides critical links in the delivery of health care to pediatric oncology patients.
Palatability and Cost Comparison of Five Liquid Corticosteroid Formulations
Authors: Hutto C.J. , Bratton Tammy H.
Published: October 2007

Difficulty administering oral corticosteroids to young children who are required to take these medications as part of their cancer treatment has been a concern among health care providers for many years. This problem is due in part to the bad taste associated with these preparations. Palatability is important to consider when prescribing a liquid corticosteroid. Seven members of a nursing research group in an academic pediatric setting evaluated palatability based on taste, aftertaste, texture, smell, and overall reaction to five different liquid corticosteroid formulations. These formulations included Pediapred® (Medeva Pharmaceuticals, Rochester, NY), Prelone® (Muro Pharmaceuticals, Tewksbury, MA), prednisone oral solution, prednisone intensol, and prednisone 10-mg tablet crushed in 10 mL of cherry syrup. The cost of each formulation was based on the cost to the participating institution. The results showed that the most palatable corticosteroid liquid formulation was also the most cost efficient. The results of this simple study have the potential to influence prescribing habits and provide caregivers with a palatable, cost-efficient corticosteroid liquid formulation.
Management of Bipolar Disorder in the Acute and Maintenance Settings
Authors: Baldassano Claudia F.
Published: October 2007

Bipolar disorder is a devastating condition that affects approximately 3% of the population. Diagnosis of bipolar disorder is often confounded by the lack of insight patients have into their manic episodes; the end result is that many patients are not diagnosed until years after their first episode and receive no treatment or inappropriate treatment in the interim. Once the diagnosis is made, medication must be chosen that can control symptoms in the short term and prevent relapse in the long term. Medication tolerability affects treatment adherence and thus determines whether a medication will be effective, especially in the long-term maintenance phase of treatment. Thus, medication tolerability has important implications for the management of bipolar disorder because of the chronic nature of the disease and the need for long-term therapy.J Am Psychiatr Nurses Assoc, 2007; 13(S5), S16-S22. DOI: 10.1177/1078390307305790
Masculine Socialization and Sexual Risk Behaviors among Black Men Who Have Sex with Men
Authors: Malebranche David J. , Fields Errol L. , Bryant Lawrence O. , Harper Shaun R.
Published: October 2007

Aspects of masculine socialization among Black men who have sex with men (MSM) and potential corresponding influences on high-risk sexual behaviors are explored in this study. Individual interviews were conducted with 29 Black MSM in Atlanta, Georgia. Findings included (1) formative masculine socialization experiences marked by an absence of biological fathers and Black male role models, (2) negative perceptions of “gay” identities and communities, (3) race and racial identification as intersecting influences on masculine and sexual identities, (4) the influences of masculine socialization and beliefs on partner selection and sexual behaviors, and (5) general themes of trust, control, “heat of the moment” sex, and low self-love as primary factors influencing condom use. Implications for future research and HIV prevention efforts targeting Black MSM are discussed.
Progress Towards The Eradication of Dracunculiasis
Authors: Pilotto Laura , Gorski June
Published: October 2007

In 1980 the World Health Organization instituted the Decade of Safe Water and Sanitation. As part of that initiative new impetus was given to programmes which dealt with the eradication of dracunculiasis. This paper, based on the review of several studies, discusses the nature of the disease, its impact upon the affected population, the possible solutions, and the progress accomplished thus far in several African nations. The use of health education is advocated as a major contributor towards the eradication of dracunculiasis.
Stiffness Identification and Tearing Analysis for Coated Membranes under Biaxial Loads
Authors: Szostkiewicz C. , Hamelin P.
Published: October 2007

In the first part of this paper, we have developed a mixed numerical and experimental method for the evaluation of the in-plane stiffness matrix of coated fabrics used in tensile architecture and submitted to biaxial loading. The evaluation of the stress distribution on cross-shaped samples is conducted with a finite element analysis soft ware.

In the second part, we have observed and analysed failure mechanisms of previously ripped samples, particularly by the evaluation of the influence of the crack length and direction on its propagation with uniaxial and biaxial tests.
Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation
Authors: Schade Andrew E. , Schieven Gary L. , Townsend Robert , Jankowska Anna M. , Susulic Vojkan , Zhang Rosemary , Szpurka Hadrian , Maciejewski Jaroslaw P.
Published: October 2007

Dasatinib is an oral small molecule inhibitor of Abl and Src family tyrosine kinases (SFK), including p56Lck (Lck). Given the central importance of Lck in transmitting signals from the T-cell receptor (TCR) signaling complex and the potent ability of dasatinib to inhibit Lck activity, we hypothesized this agent could provide a novel route of immunomodulation via targeted inhibition of antigen-induced signaling. Herein, we show that dasatinib inhibits TCR-mediated signal transduction, cellular proliferation, cytokine production, and in vivo T-cell responses. However, dasatinib-mediated inhibition does not induce apoptosis because the effect is reversible or may be overcome by signals bypassing the TCR, such as phorbol ester. Signal transduction and proliferative responses via IL-2 remain essentially unperturbed, suggesting that dasatinib displays specificity for TCR signaling. In addition, dasatinib combined with cyclosporine A or rapamycin led to a much more potent inhibition of T-cell activation, suggesting that targeted inhibition of Lck could be a useful adjunct for enhanced immunomodulation. In combination with currently available immunomodulatory agents, SFK inhibition could potentially increase immunomodulatory efficacy while minimizing toxicity of individual agents.
Phase 1 trial and pharmacokinetic study of arsenic trioxide in children and adolescents with refractory or relapsed acute leukemia, including acute promyelocytic leukemia or lymphoma
Authors: Fox Elizabeth , Razzouk Bassem I. , Widemann Brigitte C. , Xiao Shaun , O'Brien Michelle , Goodspeed Wendy , Reaman Gregory H. , Blaney Susan M. , Murgo Anthony J. , Balis Frank M. , Adamson Peter C.
Published: October 2007

Arsenic trioxide (ATO) induces remission in 85% of adults with refractory acute promyelocytic leukemia (APL). We conducted a phase 1 trial of ATO in children (median age 13 y, range, 2-19) with refractory leukemia. ATO was administered intravenously over 2 hours, 5 d/wk for 20 doses/cycle. Patients with APL (n = 13) received 0.15 mg/kg per day, and patients with other types of leukemia received 0.15 mg/kg per day (n = 2) or 0.2 mg/kg per day (n = 4). Nineteen of the 24 enrolled patients were fully evaluable for toxicity. At 0.15 mg/kg per day, 2 of 15 patients experienced dose-limiting corrected QT interval (QTc) prolongation, pneumonitis, or neuropathic pain. At 0.2 mg/kg per day, 2 of 4 patients had dose-limiting QTc prolongation or pancreatitis. Non–dose-limiting toxicities included elevated serum transaminases, nausea, vomiting, abdominal pain, constipation, electrolyte imbalance, hyperglycemia, dermatitis, and headache. At 0.15 mg/kg per day, the median (range) plasma arsenic maximum concentration (Cmax) was 0.28 μM (0.11-0.37 μM) and at 0.2 mg/kg per day, Cmax was 0.40 and 0.46 μM; area under the concentration times time curve (AUC0-24) was 2.50 μM-hr (1.28-3.85 μM-hr) and 4.37 μM-hr and 4.69 μM-hr, respectively. Morphologic complete response (CR) was achieved in 85% of patients with APL; no responses were observed in non-APL patients. ATO is well-tolerated in children at the recommended dose of 0.15 mg/kg per day. The response rate in children with relapsed APL is similar to the response rate in adults. This trial was registered as #NCT00020111 at www.ClinicalTrials.gov.
Fine specificity of drug-dependent antibodies reactive with a restricted domain of platelet GPIIIA
Authors: Peterson Julie A. , Nelson Tamara N. , Kanack Adam J. , Aster Richard H.
Published: October 2007

Drug-induced immune thrombocytopenia is caused by drug-dependent antibodies (DDAbs) that bind tightly to platelet glycoproteins only when drug is present. How drugs mediate this interaction is not yet resolved. Several studies indicate that sites recognized by DDAbs tend to cluster in specific structural domains, suggesting they may recognize a limited number of distinct epitopes. To address this issue, we characterized the binding sites for 16 quinine-dependent antibodies thought on the basis of preliminary studies to be possibly specific for a single epitope on glycoprotein IIIa (GPIIIa). Fourteen of the antibodies reacted with a 29-kDa GPIIIa fragment comprising only the GPIIIa hybrid and plextrin-semaphorin-integrin homology domains. However, studies with mutant GPIIIa and the blocking monoclonal antibody AP3 showed that the 14 DDAbs recognize at least 6 and possibly more distinct, but overlapping, structures involving GPIIIa residues 50 to 66. The findings suggest that even antibodies specific for restricted domains on a target glycoprotein may each have a slightly different fine specificity; ie, “unique” epitopes recognized by DDAbs may be rare or nonexistent. The observations are consistent with a recently proposed model in which drug reacts noncovalently with both target protein and antibody to promote binding of an otherwise nonreactive immunoglobulin.
Global expression analysis of nucleotide binding site-leucine rich repeat-encoding and related genes in Arabidopsis
Authors: Tan Xiaoping , Meyers Blake C , Kozik Alexander , West Marilyn AL , Morgante Michele , St Clair Dina A , Bent Andrew F , Michelmore Richard W
Published: October 2007

Background

Nucleotide binding site-leucine rich repeat (NBS-LRR)-encoding genes comprise the largest class of plant disease resistance genes. The 149 NBS-LRR-encoding genes and the 58 related genes that do not encode LRRs represent approximately 0.8% of all ORFs so far annotated in Arabidopsis ecotype Col-0. Despite their prevalence in the genome and functional importance, there was little information regarding expression of these genes.

Results

We analyzed the expression patterns of ~170 NBS-LRR-encoding and related genes in Arabidopsis Col-0 using multiple analytical approaches: expressed sequenced tag (EST) representation, massively parallel signature sequencing (MPSS), microarray analysis, rapid amplification of cDNA ends (RACE) PCR, and gene trap lines. Most of these genes were expressed at low levels with a variety of tissue specificities. Expression was detected by at least one approach for all but 10 of these genes. The expression of some but not the majority of NBS-LRR-encoding and related genes was affected by salicylic acid (SA) treatment; the response to SA varied among different accessions. An analysis of previously published microarray data indicated that ten NBS-LRR-encoding and related genes exhibited increased expression in wild-type Landsberg erecta (Ler) after flagellin treatment. Several of these ten genes also showed altered expression after SA treatment, consistent with the regulation of R gene expression during defense responses and overlap between the basal defense response and salicylic acid signaling pathways. Enhancer trap analysis indicated that neither jasmonic acid nor benzothiadiazole (BTH), a salicylic acid analog, induced detectable expression of the five NBS-LRR-encoding genes and one TIR-NBS-encoding gene tested; however, BTH did induce detectable expression of the other TIR-NBS-encoding gene analyzed. Evidence for alternative mRNA polyadenylation sites was observed for many of the tested genes. Evidence for alternative splicing was found for at least 12 genes, 11 of which encode TIR-NBS-LRR proteins. There was no obvious correlation between expression pattern, phylogenetic relationship or genomic location of the NBS-LRR-encoding and related genes studied.

Conclusion

Transcripts of many NBS-LRR-encoding and related genes were defined. Most were present at low levels and exhibited tissue-specific expression patterns. Expression data are consistent with most Arabidopsis NBS-LRR-encoding and related genes functioning in plant defense responses but do not preclude other biological roles.
Functional polymorphisms in the promoter regions of MMP2 and MMP3 are not associated with melanoma progression
Authors: Cotignola Javier , Roy Pampa , Patel Ami , Ishill Nicole , Shah Shivang , Houghton Alan , Coit Daniel , Halpern Allan , Busam Klaus , Berwick Marianne , Orlow Irene
Published: October 2007

Background

The matrix metalloproteinases (MMPs) are enzymes that cleave various components of the extracellular matrix (ECM) and basement membranes. MMPs are expressed in melanocytes and their overexpression has been linked to tumor development, progression and metastasis. At the genetic level, the following functional promoter polymorphisms are known to modify the gene transcription: -1306 C/T and -735 C/T in the MMP2 gene, and -1171 5A/6A in the MMP3 gene. Functional polymorphisms in MMP genes' promoter regions may modulate the risk for melanoma progression.

Methods

We evaluated MMP2 and MMP3 germline polymorphisms in a group of 1002 melanoma patients using PCR-based methods, including fragment size analysis and melting temperature profiles. Two-sided Chi-Square, Cochran-Armitage tests for trend, Fisher's exact tests, and Kendall's Tau tests were performed to evaluate the associations between genotype and various clinical and epidemiologic factors. Multivariate analyses were conducted using logistic regression, adjusting for known melanoma confounders such as age, sex, phenotypic index, moles, freckles, and race. Survival estimates were computed using the Kaplan-Meier method and differences in survival were assessed using the log rank test.

Results

All genotypes were in Hardy-Weinberg equilibrium. After adjustment for age, sex and phenotypic characteristics of melanoma risk, no significant associations were identified with the clinical, pathological, and epidemiological variables studied. The melting profile for MMP2 -735 C/T identified a new change in one sample. A new PCR-amplification followed by direct sequencing confirmed a heterozygote G to A substitution at position -729.

Conclusion

This study does not provide strong evidence for further investigation into the role of the MMP2 and MMP3 variants in melanoma progression.
Genetic incorporation of the protein transduction domain of Tat into Ad5 fiber enhances gene transfer efficacy
Authors: Han Tie , Tang Yizhe , Ugai Hideyo , Perry Leslie E , Siegal Gene P , Contreras Juan L , Wu Hongju
Published: October 2007

Background

Human adenovirus serotype 5 (Ad5) has been widely explored as a gene delivery vector for a variety of diseases. Many target cells, however, express low levels of Ad5 native receptor, the Coxsackie-Adenovirus Receptor (CAR), and thus are resistant to Ad5 infection. The Protein Transduction Domain of the HIV Tat protein, namely PTDtat, has been shown to mediate protein transduction in a wide range of cells. We hypothesize that re-targeting Ad5 vector via the PTDtat motif would improve the efficacy of Ad5-mediated gene delivery.

Results

In this study, we genetically incorporated the PTDtat motif into the knob domain of Ad5 fiber, and rescued the resultant viral vector, Ad5.PTDtat. Our data showed the modification did not interfere with Ad5 binding to its native receptor CAR, suggesting Ad5 infection via the CAR pathway is retained. In addition, we found that Ad5.PTDtat exhibited enhanced gene transfer efficacy in all of the cell lines that we have tested, which included both low-CAR and high-CAR decorated cells. Competitive inhibition assays suggested the enhanced infectivity of Ad5.PTDtat was mediated by binding of the positively charged PTDtat peptide to the negatively charged epitopes on the cells' surface. Furthermore, we investigated in vivo gene delivery efficacy of Ad5.PTDtat using subcutaneous tumor models established with U118MG glioma cells, and found that Ad5.PTDtat exhibited enhanced gene transfer efficacy compared to unmodified Ad5 vector as analyzed by a non-invasive fluorescence imaging technique.

Conclusion

Genetic incorporation of the PTDtat motif into Ad5 fiber allowed Ad5 vectors to infect cells via an alternative PTDtat targeting motif while retaining the native CAR-mediated infection pathway. The enhanced infectivity was demonstrated in both cultured cells and in in vivo tumor models. Taken together, our study identifies a novel tropism expanded Ad5 vector that may be useful for clinical gene therapy applications.
American ginseng modulates pancreatic beta cell activities
Authors: Wu Zonggui , Luo John Zeqi , Luo Luguang
Published: October 2007

The mechanism of the beneficial effects of Panax quinquefolius (Xiyangshen, American ginseng) on diabetes is yet to be elucidated. Recent studies show that Panax quinquefolius increases insulin production and reduces the death of pancreatic beta cells. Mechanism studies indicate that Panax quinquefolius improves cell's immuno-reactivity and mitochondrial function through various factors. Clinical studies show that Panax quinquefolius improves postprandial glycemia in type 2 diabetic patients. Further studies to identify the component(s) of Panax quinquefolius linked with pancreatic islets/beta cells in vitro and in vivo are warranted for better understanding of the full effects of Panax quinquefolius.
Prostate-specific antigen, sexual behavior, and sexually transmitted infections in US men 40–59 years old, 2001–2004: a cross – sectional study
Authors: Werny David M , Saraiya Mona , Chen Xiao , Platz Elizabeth A
Published: October 2007

Background

Sexually transmitted infections (STIs) are hypothesized to play a role in the development of prostate cancer, perhaps due to inflammation-induced oncogenesis. We assessed in a nationally representative population of middle-aged men whether sexual behavior indicators for an increased risk of genital infection were associated with serum prostate-specific antigen (PSA) concentration, a marker of prostatic disease and inflammation.

Results

The percentage of men between the ages of 40 and 59 with a PSA ≥ 4.0 ng/ml was 2.6% (95% confidence interval [CI], 1.8% – 3.8%). The percentage of men between the ages of 40 and 59 self-reporting a past diagnosis of genital warts or genital herpes, or a recent diagnosis of gonorrhea or chlamydia is estimated to be 7.3% (95% CI, 6.2% – 8.6%). Men self-reporting that they had had sex without using a condom in the past month had a lower PSA concentration and higher %fPSA than those who did not. There were no associations between any of the other sexual activity or laboratory measures and PSA or %fPSA.

Conclusion

In this nationally representative sample of middle-aged American men, we did not find consistent evidence for an association between sexual behavior or a history of STIs and PSA levels. Therefore, sexual factors are unlikely to lead to falsely elevated PSA tests in this population. We cannot rule out the role of these factors in causing false positive PSA tests in subgroups of the population that have a higher prevalence of high-risk sexual behavior, and more protracted or recent exposures to these agents.
Serum Levels of the Adipokine Vaspin in Relation to Metabolic and Renal Parameters
Authors: Seeger Jeannette , Ziegelmeier Michaela , Bachmann Anette , Lössner Ulrike , Kratzsch Jürgen , Blüher Matthias , Stumvoll Michael , Fasshauer Mathias
Published: October 2007

Context: Recently, vaspin was identified as an insulin-sensitizing adipokine. However, regulation of this adipocyte-secreted factor in human disease has not been determined.

Objective: We investigated vaspin serum concentrations in diabetic and nondiabetic patients on chronic hemodialysis (CD) as compared with controls with a glomerular filtration rate (GFR) above 50 ml/min.

Design: Vaspin was quantified by ELISA in control (n = 60) and CD (n = 60) patients and correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation, in both groups.

Results: Mean serum vaspin concentrations were not significantly different between CD patients and controls. Circulating vaspin was significantly lower in males (0.6 ± 0.9 μg/liter) as compared with females (1.3 ± 1.5 μg/liter) and was decreased in insulin-treated subjects. In univariate analyses, vaspin levels positively correlated with age and high-density lipoprotein cholesterol and negatively with waist-to-hip ratio and GFR in control patients, whereas the adipokine was negatively associated with GFR and C-reactive protein (CRP) in CD patients. In multivariate analyses, age and gender were independently associated with vaspin in controls, whereas gender, GFR, and CRP independently predicted circulating vaspin in CD patients.

Conclusions: Vaspin levels are significantly higher in women, and gender is an independent predictor of circulating vaspin in both control and CD patients. In addition, age independently predicts vaspin in control patients, whereas GFR and CRP are independently associated with this adipokine in CD patients. In contrast, circulating vaspin is not independently associated with markers of glucose and lipid metabolism.
Heparanase cleavage of perlecan heparan sulfate modulates FGF10 activity during ex vivo submandibular gland branching morphogenesis
Authors: Patel Vaishali N. , Knox Sarah M. , Likar Karen M. , Lathrop Colin A. , Hossain Rydhwana , Eftekhari Siavash , Whitelock John M. , Elkin Michael , Vlodavsky Israel , Hoffman Matthew P.
Published: October 2007

Heparan sulfate proteoglycans are essential for biological processes regulated by fibroblast growth factors (FGFs). Heparan sulfate (HS) regulates the activity of FGFs by acting as a coreceptor at the cell surface, enhancing FGF-FGFR affinity, and being a storage reservoir for FGFs in the extracellular matrix (ECM). Here we demonstrate a critical role for heparanase during mouse submandibular gland (SMG) branching morphogenesis. Heparanase, an endoglycosidase, colocalized with perlecan in the basement membrane and in epithelial clefts of SMGs. Inhibition of heparanase activity in organ culture decreased branching morphogenesis, and this inhibition was rescued specifically by FGF10 and not by other FGFs. By contrast, exogenous heparanase increased SMG branching and MAPK signaling and, surprisingly, when isolated epithelia were cultured in a three-dimensional ECM with FGF10, it increased the number of lateral branches and end buds. In a solid-phase binding assay,an FGF10-FGFR2b complex was released from the ECM by heparanase. In addition,surface plasmon resonance (SPR) analysis showed that FGF10 and the FGF10-FGFR2b complex bound to purified perlecan HS and could be released by heparanase. We used the FGF10-FGFR2b complex as a probe for HS in SMGs, and it colocalized with perlecan in the basement membrane and partly colocalized with syndecan 1 in the epithelium, and binding was reduced by treatment with heparanase. In summary, our results show heparanase releases FGF10 from perlecan HS in the basement membrane, increasing MAPK signaling, epithelial clefting, and lateral branch formation, which results in increased branching morphogenesis.
RILP is required for the proper morphology and function of late endosomes
Authors: Progida Cinzia , Malerød Lene , Stuffers Susanne , Brech Andreas , Bucci Cecilia , Stenmark Harald
Published: October 2007

Lysosomal degradation of signalling receptors such as the epidermal growth factor (EGF) receptor (EGFR) is an important mechanism for termination of cell signalling. Such degradation involves the endosomal sorting of ubiquitylated receptors into intralumenal vesicles (ILVs) of multivesicular endosomes (MVEs) that move along microtubules to fuse with perinuclear lysosomes. The Rab7-interacting lysosomal protein RILP is interesting in this context as it interacts with Vps22 (also known as EAP30) and Vps36 (also known as EAP45), subunits of the endosomal sorting complex required for transport II (ESCRT-II), as well as with the dynein-dynactin motor complex. Because previous functional studies of RILP have been based on its overexpression, we have asked here whether RILP is required for endocytic trafficking of receptors. Depletion of RILP caused elevated levels of four late-endosomal molecules, lyso-bisphosphatidic acid, Lamp1, CD63 and cation-independent mannose-6-phosphate receptors. Electron microscopy showed that endosomes of RILP-depleted cells were morphologically distinct from normal late endosomes and had a strongly reduced content of ILVs. As in Vps22-depleted cells, ligand-mediated degradation of EGFRs was strongly inhibited in RILP-depleted cells, in which endocytosed EGFRs were found to accumulate in early endosomes. By contrast, endocytosis and recycling of transferrin receptors occurred normally in RILP-depleted cells. These results establish that RILP, like the ESCRT proteins, is required for biogenesis of MVEs and degradative trafficking of EGFRs but not for trafficking of transferrin receptors through early endosomes. We propose that RILP might coordinate the biogenesis of MVEs with dynein-mediated motility.