bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitory Action of a Novel Proton Pump Inhibitor, Rabeprazole, and its Thioether Derivative Against the Growth and Motility of Clarithromycin‐Resistant Helicobacter pylori
Authors: Ohara Tatsuki , Goshi Satoshi , Taneike Ikue , Tamura Yukiko , Zhang Hui‐Min , Yamamoto Tatsuo
Published: March 2003

Background.

 Clarithromycin‐resistant Helicobacter pylori (CRHP) has increasingly been isolated from patients in Japan. The aim of our study was to test whether proton pump inhibitors (PPIs) and their thioether derivatives, which are secreted into the gastric mucosa, could inhibit the growth and motility (a factor in colonization) of CRHP.

Materials and Methods.

 CRHP was isolated from patients who had experienced gastritis or peptic ulcers in Tokyo and Niigata. Drugs and related agents tested were omeprazole, lansoprazole, rabeprazole, the thioether derivative of rabeprazole (rabeprazole‐TH), clarithromycin, amoxicillin and metronidazole. The MICs of the drugs and agents for H. pylori strains were determined by the agar dilution method. Bacterial swimming in a liquid layer was examined under an inverted, phase‐contrast microscope.

Results.

 The PPIs and rabeprazole‐TH, but not the anti‐H. pylori agents, inhibited the motility of CRHP at both pH 7.4 and 6.0. The concentrations (µg/ml) necessary to inhibit 50% of the motility at pH 7.4 were 0.25–0.5, 8–32, 8–16 and 128–256 for rabeprazole‐TH, rabeprazole, lansoprazole and omeprazole, respectively. Rabeprazole‐TH exibited the strongest inhibitory effect against the growth of CRPH (MIC, 0.5 µg/ml).

Conclusion.

 Rabeprazole‐TH, which is secreted into the gastric mucosa, had the strongest inhibitory action against both the growth and motility of CRHP, suggesting that it is a potential novel agent for CRHP eradication.
Normalization of Phospholipids Concentration of the Gastric Mucosa was Observed in Patients with Peptic Ulcer after Eradication of Helicobacter pylori
Authors: Ishibashi Sadatoshi , Iwakiri Ryuichi , Shimoda Ryo , Ootani Hibiki , Kawasaki Seiji , Tadano Jutarou , Kikkawa Atsushi , Ootani Akifumi , Oda Kayoko , Fujise Takehiro , Yoshida Toshifumi , Tsunada Seiji , Sakata Hiroyuki , Fujimoto Kazuma
Published: March 2003

Background. Phospholipids concentration in the gastric mucosa decreased in patients with Helicobacter pylori infection. The aim of this study is to examine the effects of eradication of H. pylori on decreasing the phospholipids concentration in the gastric mucosa in patients with gastric or duodenal ulcer.

Materials and Methods. Phospholipids (phosphatidylcholine, phosphatidylethanolamine, and sphingonomyeline) were measured in biopsy specimens from the antrum and corpus using thin‐layer chromatography. In H. pylori positive patients with gastric ulcer (n = 26) and duodenal ulcer (n = 13), and H. pylori negative controls (n = 20), the biopsy specimens were obtained before and 3 months after eradication. Eradication was performed using lansoprazole, amoxycillin, and clarithromycin.

Results. Compared with the H. pylori negative control group, the concentrations of phosphatidylcholine and phosphatidylethanolamine decreased significantly in the gastric ulcer group in both antrum and corpus mucosa, and in the duodenal ulcer group in antrum mucosa. This decrease returned to the control level after eradication.

Conclusions. This study demonstrates that the eradication of H. pylori in patients with peptic ulcer normalized the decrease of phosphatidylcholine and phosphatidylethanolamine in the gastric mucosa.
Helicobacter pylori: the challenge in therapy
Authors: Bazzoli Franco , Pozzato Paolo , Rokkas Theodore
Published: March 2003

For the therapeutic management of Helicobacter pylori infection, the Maastricht 2–2000 Consensus Report have introduced the concept of the ‘treatment package’ that considers first‐ and second‐line eradication therapies together. According to this consensus statement, the first‐line therapy for H. pylori eradication is a combination of the proton pump inhibitors (PPI) or ranitidine bismuth citrate (RBC) and claritromycin plus either amoxicillin or metronidazole. The second‐line treatment is suggested to be PPI‐quadruple therapy for a minimum of 7 days. If bismuth compounds are not available, PPI‐based triple therapy will have to be used as a second‐line treatment only after susceptibility testing. Since no considerable progress has been made during the past year in treatment regimens, there is still a need for new compounds that are specific for H. pylori, which could constitute future therapies.
Improving Pain Relief in a Rural Cancer Center
Authors: Baltic Tammy E. , Whedon Marie Bakitas , Ahles Tim A. , Fanciullo Gilbert
Published: March 2003

purpose: The purpose of this article is to describe barriers to cancer pain management and strategies for making improvements in an academic rural cancer center.

overview: Rural communities pose unique challenges to cancer pain management because of their unique strengths and burdens. Successful strategies used by a comprehensive cancer center to improve pain management in rural New England are summarized.

clinical implications Improving cancer pain management in a rural setting required a recognition of the contrasting characteristics between a sophisticated academic medical center and a rural community. The successful implementation of quality improvement strategies required a combination of leadership support, internal and external funding, and professional and federal recognition of the problem. Using a quality improvement approach rather than a traditional didactic approach, and fostering communication, trust, and collegiality at our outreach sites were pivotal to our success.
Knowledge and Practices Among Korean Americans
Authors: Kim Katherine , Yu Elena S. H. , Chen Edwin H. , Kim JaeKyung , Brintnall Ruth Ann
Published: March 2003

purpose
: The purpose of this study was to examine knowledge and practices of colorectal cancer screening among Korean Americans.

description of study: The sample consisted of 104 Korean American men and 159 women, 40 to 69 years of age, living in the Chicago area. The National Health Interview Survey (NHIS) Cancer Control Supplement Questionnaire, prepared by the National Center for Health Statistics, was used to collect data regarding colorectal cancer screening knowledge and practices. The NHIS questionnaire was translated into Korean with minor modification.

results
: The percentages of male respondents ever having had a digital rectal exam (DRE) and fecal occult blood test (FOBT) were 13.5% and 10.6%, respectively. Only 11.3% of women reported DRE and 8. 8% FOBT. Multiple logistic regression analysis results indicate that gender, education, knowledge of the seven cancer warning signals, and length of residence in the United States were significantly related to having heard of DRE. For those having had DRE, knowledge of the seven cancer warning signals, and length of residence in the United States were the only significant variables. Gender and education were significantly related to having heard of FOBT. None of the variables were found to be significantly related to having had FOBT. The findings indicate that a majority of respondents were unaware of these cancer screening examinations and forego these tests due to an underestimation of their importance.

clinical implications
: The findings of this study underscore the importance of cancer education and further research addressing the cancer screening needs of Korean Americans. Currently, Korean Americans do not see healthcare providers or health brochures as valuable sources of health information. Therefore, healthcare professionals need to target this population by 1) co‐ordinating their efforts with church and other community leaders and 2) developing health brochures that are in the Korean language and sensitive to the Korean culture.
Cost Considerations as Potential Barriers to Cancer Treatment
Authors: Guidry Jeffrey J. , Aday Lu Ann , Zhang Dong , Winn Rodger J.
Published: March 2003

purpose
: An analytical cross‐sectional survey was conducted to determine the prevalence of barriers to cancer treatment in Texas as perceived by diagnosed cancer patients. Results reported here address the role of insurance coverage, indirect costs (transportation, lodging, and work days lost), and direct costs of care as barriers to treatment for white, black, and Hispanic cancer patients. Specific objectives of the analyses undertaken here are to examine 1) racial/ethnic differences in insurance coverage; 2) barriers relating to insurance coverage experienced by cancer patients; and 3) role of treatment‐related costs as barriers to cancer treatment.

description of study
: A mail questionnaire was developed to assess the perceived barriers to cancer treatment in Texas for adult cancer patients, 17 years and older, who had been diagnosed with breast, colon, cervical, prostate, or lymphoma during the period of 1989 to 1993. The sampling frame for this study was obtained from a network of cancer treatment facilities throughout the state of Texas within the University of Texas M.D. Anderson Cancer Center Texas Community Oncology Network. A total of 593 cancer patients returned their surveys, yielding a 65.2% response rate. Weighting adjustments were then made to correct for differential sampling and response rates by racial groupings and type of cancer. All of the analyses used adjusted weights.

results
: The findings document the financial considerations (insurance, direct and indirect costs) as they relate to barriers to cancer treatment. Specific insurance premium‐related barriers with regard to maintaining and affording coverage were more prevalent for blacks. Hispanics were less likely to have insurance coverage; however, more blacks reported being denied insurance coverage when they changed jobs compared with whites and Hispanics. Minorities, particularly Hispanics, were more likely to have experienced cost‐related barriers associated with medications, diagnostic tests, and hospitalizations. In addition, Hispanics experienced significant out‐of‐pocket costs in paying for cancer treatment.

clinical implications
: This research shows the need for staff at cancer treatment facilities to be aware that there are nonclinical, financial factors that are important considerations in the treatment of cancer patients. Assessment of cancer patients during the diagnostic and treatment stages, possibly through case management, will provide information on potential barriers to treatment for individual patients. Hospital programs that reimburse out‐of‐pocket costs, transportation costs to obtain services, and lodging accommodations may be available. Additional services may be offered through cancer advocacy groups, such as the American Cancer Society and the National Coalition for Cancer Survivors, to assist patients with managing costs and overcoming barriers to care.
Side effects of cyclophosphamide, methotrexate, and 5‐fluorouracil (CMF) chemotherapy for breast cancer.
Authors: Sitzia J , Huggins L
Published: March 2003

PURPOSE: The purpose of this study was to describe the range of side effects experienced by a sample of patients receiving six cycles of cyclophosphamide, methotrexate, 5‐fluorouracil (CMF) chemotherapy in the treatment of breast cancer. The study aimed to document the incidence and severity of side effects after each cycle of treatment and to determine which side effects patients perceived as most "troublesome." DESCRIPTION OF STUDY: A sample of 52 women receiving chemotherapy on an outpatient basis completed a reliable and valid self‐ report questionnaire after each treatment cycle. The questionnaire listed 61 potential problems and prompted respondents to note any unlisted problems that they had experienced. Respondents assessed the severity of each problem on a five‐point adjectival scale. The participants provided a total of 260 questionnaires assessable for data analysis. RESULTS: A total of 94 different side effects were reported. The most commonly reported problem was alopecia (mean incidence = 91%), followed by fatigue (89%), and weight gain (68%). Postchemotherapy nausea ranked 12th in terms of incidence. However, in response to an open question, patients judged fatigue and nausea to be the "most troublesome" problems, followed by difficulty sleeping and sore eyes. CLINICAL IMPLICATIONS: A most important implication of these findings is that the incidence of a side effect is not a reliable guide to the significance of the problem in terms of patient well‐being; alopecia may be the most common problem identified, but it does not appear to be the problem that is most troublesome to patients. To further understand and alleviate the side effects of chemotherapy, the following measures are necessary. Patient education should be based on detailed, regimen‐ specific information. Routine, systematic assessment of the individual patient's side effects is desirable. Because many side effects appear to be controlled only moderately, healthcare providers must work toward more sophisticated, holistic symptom management strategies.
Factors Hindering Patients' Use of Medications for Cancer Pain Factors Hindering Patients' Use of Medications for Cancer Pain
Authors: Ersek Mary , Miller Kraybill Beth , Du Pen Anna
Published: March 2003

objectives: The purpose of this study was to explore the reasons that cancer patients with pain find it difficult to adhere to analgesic therapy.

materials and methods: Twenty‐one patients with advanced cancer with pain were interviewed using a semistructured schedule of questions. Participants were asked to describe their decision making regarding analgesics and the factors that made it difficult for them to take analgesics prescribed for their pain. They also were asked to describe their relationships with their healthcare providers. Themes were identified and refined using qualitative analytic techniques. Two investigators independently coded all data to ensure that findings accurately reflected participants' experiences.

results: Findings reveal several factors that hindered analgesic use and the specific ways in which patients evaluated these factors in making decisions about taking pain medication. The provider‐patient factors that impeded analgesic use also were described. Finally, the common use of nonpharmacologic methods of pain control offers insight into the role of these therapeutic strategies in achieving pain relief and decreasing analgesic use.

conclusions: The findings underscore the importance of early intervention to address barriers to analgesic use. Some barriers may be overcome through educational efforts. The findings suggest, however, that consistent, repeated patient education often may not be sufficient to subdue patients' negative thoughts about taking the medication. Other approaches, such as changing medications or assisting the patient to use nonpharmacologic pain strategies, may prove more successful.
Body Image and Quality of Life After Head and Neck Cancer Surgery
Authors: Dropkin Mary jo
Published: March 2003

objectives: The purpose of this paper is to describe the process of body image reintegration as it relates to quality of life in the surgical head and neck cancer patient.

materials and methods: To illustrate the course of body image reintegration after head and neck cancer surgery, the results of two major studies are presented. In the first study, a cohort sample of 75 adults about to undergo disfigurative surgery for head and neck cancer was examined to determine levels of anxiety before and after the procedure. The State Trait Anxiety Inventory was administered before and after surgery on postoperative days 4 through 6. In the large study, from which the cohort sample was derived, 117 adults about to undergo disfigurative surgery were investigated to determine the relationship between coping with surgical disfigurement/dysfunction and length of hospital stay. The Ways of Coping Checklist was administered before surgery. Disfigurement/dysfunction, as measured by the Disfigurement/Dysfunction Scale, and postoperative coping behaviors, as measured by the Coping Behaviors Score, were accounted for in both samples. Self‐care and resocialization behaviors were observed and measured on postoperative days 4 through 6.

results: In the cohort study, anticipation of disfigurative facial surgery was associated with extremely high levels of anxiety. In the large sample, coping effectiveness was diminished. The degree of surgical deficit ranged from mild to severe disfigurement and dysfunction. Preoperative coping effectiveness predicted postoperative coping behavior. It was concluded that body image reintegration was characterized by self‐care, resocialization, and reduced anxiety. Further, that these components, when taken together, constitute assimilation of the surgical defect into self.

conclusions: Body image reintegration is critical to subsequent quality of life after head and neck cancer surgery. When disfigurement/dysfunction is associated with treatment, quality of life may be profoundly and adversely affected. Findings from the studies presented indicate a significant correlation between postoperative self‐care and reduction in level of anxiety. The implications of this finding are important to care during the early period after surgery and to long‐term follow‐up after hospital discharge.
Cognition and The Cancer Experience
Authors: Foster Larry W. , McLellan Linda
Published: March 2003

Objectives: The authors demonstrate the application of cognitive therapy in oncology care by presenting a brief review of theory and relevant case studies.

Materials and methods: In light of the life and death nature of the fears evoked by cancer, it is important for the oncology clinician to recognize the role that cognition plays in patient responses to the diagnosis and treatment of cancer. After presentation of a theory base that creatively links cognition and the cancer experience, key cognitive concepts are defined and discussed. Case material illustrates the application of these concepts and how oncology clinicians can use select interventions adapted from the brief mental health treatment modality of cognitive therapy to promote adjustment to cancer.

Results: Patient and family views about cancer have emotional and behavioral consequences, influence ability to cope with diagnosis and treatment, and serve to focus clinical intervention. Cognitive interventions can help patients and families think about cancer in objective, adaptive ways. Focusing on perceptions and questions of meaning, clinicians can be effective using cognitive lines of questioning that expand patient stories and elicit beliefs about cause, control, and responsibility for their cancer.

Conclusions: Cognitive interventions are brief and solution‐focused interventions that acknowledge and build on generalist interviewing skills common to each discipline. As such, they are particularly useful in physical health settings where work is fast paced and clinicians are faced with the challenge of dealing in a collaborative manner with patient and family coping responses as they apply to the medical problem and care plan.
Caregiver Responses and Needs
Authors: Grimm Patricia M. , Zawacki Kristin L. , Mock Victoria , Krumm Sharon , Frink Barbara B.
Published: March 2003

Purpose: This longitudinal, descriptive outcomes study was conducted to compare the emotional responses and needs of the caregivers of patients who undergo bone marrow transplantation (BMT) for hematologic malignancies, as observed in an inpatient/outpatient (IPOP) setting with those in an inpatient setting.

Description of study: A convenience sample of 43 caregivers for patients undergoing either autologous or allogeneic BMT was selected from both the inpatient unit (n = 26) and the IPOP ambulatory setting (n = 17). Emotional responses were measured by the Profile of Mood States. The importance and satisfaction of informational, patient‐care, and psychological needs were assessed with the Caregiver Needs Survey, a modified version of the Home Cancer Caregiver Needs Survey. Data were collected at six points across the BMT trajectory, from before the procedure to 12 months after. Descriptive statistics were used to report sample characteristics, emotional responses, and needs. Nonparametric statistics were used to compare the IPOP and inpatient caregiver groups, and to identify relationships between emotional responses and needs within groups.

Results: IPOP caregivers were found to have significantly less mood disturbance at points before discharge. Both groups showed a decrease in mood disturbance 6 and 12 months after BMT. IPOP caregivers had higher levels of satisfaction of their informational and psychological needs at day 21. Significant correlations between total mood disturbance and satisfaction of informational, psychological, and patient‐care needs were found for inpatient caregivers across treatment time points.

Clinical implications: These findings support the IPOP model of care as being less emotionally distressing for and better meeting the needs of family caregivers. Specific implications for practice include the importance of caregiver education in the area of patient‐care information and of assessment and intervention to meet caregiver psychological needs. Continued evaluation of the impact of changes in care delivery on family caregivers is essential for the provision of comprehensive cancer care.
Monoclonal Antibody Therapy for Lymphoma
Authors: Dillman Robert O.
Published: March 2003

Purpose: The purpose of this article is to review the historical development and recent advances in the application of monoclonal antibodies for the treatment of lymphoma.

Overview: The history of clinical applications of monoclonal antibodies has been intertwined with that of lymphomas. The first report of a complete remission in 1981 described a patient with follicular lymphoma who was treated with a murine anti‐idiotype antibody. Later that decade there appeared additional encouraging reports of radiolabeled monoclonal antibodies, immunotoxins, and other antibodies with antitumor effects against lymphoma and chronic lymphocytic leukemia. Monoclonal antibodies as a treatment of malignancy became reality in late 1997 when the US Food and Drug Administration approved the anti‐CD20 chimeric monoclonal antibody rituximab for the treatment of B‐cell lymphoma. Since that time an anti‐CD25 monoclonal antibody (dacliximab) and an anti‐CD25 immunotoxin fusion product (denileukin diftitox) have become clinically available. Several radio‐ labeled antibodies, including the murine anti‐CD20 products 131I‐tositumomab and 90Y‐ibritumomab tiuxetan, are in advanced stages of clinical testing as are other unlabeled monoclonal antibodies with antilymphoma activity. Other antilymphoma immunotoxins that react with CD25, CD19, and CD22 also have shown promise.

Clinical implications: The therapeutic arsenal against lymphoma has been significantly changed by the addition of these antibody products that are active as single agents, and are synergistic, additive, or both with other antilymphoma treatments.
Identifying Support Issues of Parents of Children with Leukemia
Authors: McGrath Pam
Published: March 2003

Purpose: One of the important factors in helping both children with acute lymphoblastic leukemia (ALL) and their family members during the difficult treatment period is the support they receive. However, there is a scarcity of research that examines the adaptation to such an experience from the family's perspective. This discussion presents the findings from recent research on accessing support from the perspective of parents with a child undergoing treatment for ALL.

Description of study: A longitudinal, qualitative study informed by a phenomenological methodology. The results are taken from parent interviews undertaken during the time period from the end of induction‐remission to the end of the 5‐week period (time period T1), collected over the first year of operation of the study.

Results: The need for support was reported as intense, and offers of support tend to lessen over time. Among the sources of support noted were partners, family, friends, employers, hospital staff, and other parents in the same situation. However, community resources appeared to be lacking, underused, or both.

Clinical implications: Suggestions for support include the provision of practical assistance through appropriately trained volunteers, the involvement of a liaison person to mentor families through the initial stages of treatment, development of parent support groups, and the opportunity for families to meet children who are successfully off treatment. Such support strategies involve sensitivity to particularly vulnerable families who have limited support available and respectfulness of the variation in individual styles of accessing support.
Telephone‐Linked Care for Cancer Symptom Monitoring
Authors: Mooney Kathi H. , Beck Susan L. , Friedman Robert H. , Farzanfar Ramesh
Published: March 2003

purpose: The purpose of this pilot project was to explore the feasibility of using a telephone‐based computerized system to monitor postchemotherapy symptoms and to test the mechanism of generating alert communications to healthcare providers about symptoms that are poorly controlled.

description of study: Twenty‐seven patients with cancer participated in the study by calling the telephone‐linked care (TLC) system daily during a single cycle of chemotherapy and reporting on seven common chemotherapy‐related symptoms. Using selected symptom data, symptoms that met a preset threshold for severity generated a fax notification of the patient's symptom pattern to the physician. Patients then were interviewed about their satisfaction with TLC and about suggestions for improvement.

results: The study demonstrated that TLC is easy to learn and use and that it captures daily symptom information from patients in their homes. A majority of patients experienced symptoms that were severe enough to generate symptom‐alert faxes. Patient satisfaction with TLC was high. The technique, TLC voice, and the duration of the calls were acceptable to patients. There were few technical problems.

clinical implications: The TLC system has the potential to improve dramatically symptom monitoring and symptom care of patients with cancer at home. Further testing is needed, but the TLC chemotherapy monitoring application shows promise for improving supportive‐care service delivery for cancer patients. In its initial test, the TLC chemotherapy monitoring application has been shown to be highly acceptable to patients, able to generate useful symptom data, and able to generate faxed alerts to healthcare providers, thus improving communication about poorly controlled symptoms.
Brief review of the stylophoran debate
Authors: Ruta Marcello
Published: March 2003

The “calcichordate” theory interprets an extinct group of calcite‐plated invertebrates, the stylophorans, as chordates. In this theory, cornute stylophorans are interpreted as stem chordates, whereas mitrate stylophorans are primitive members of the acraniates, tunicates, and craniates. However, this theory discounts major synapomorphies between cornutes and mitrates. These groups constitute a natural, monophyletic group which is here argued to lie within the echinoderm radiation. The “calcichordate” theory is, therefore, rejected because it relies on assumption‐driven hypotheses of character transformation which are supported by ambiguous, poor, or missing fossil evidence. Stylophorans may lie at the base of the echinoderm clade and primitively lack pentameral symmetry, therefore casting light on the near‐ancestral body organization of the phylum.
Anteroposterior patterning by mutual repression of orthodenticle and caudal‐type transcription factors
Authors: Isaacs Harry V. , Andreazzoli Massimiliano , Slack Jonathan M. W.
Published: March 2003

SUMMARY Members of the Otx (orthodenticle) and Cdx (caudal) families of homeodomain transcription factors are expressed in similar embryonic regions in all animal groups and have been shown to be directly involved in anteroposterior patterning in a number of species. In the amphibian Xenopus laevis, the Otx family gene Xotx2 and the Cdx family gene Xcad3 are both expressed within the early dorsal organizer. We show that they have mutually repressive activities, suggesting that they play a crucial role in the early regionalization of the organizer into anterior and posterior territories. Xotx2 can act both as an activator and repressor of gene expression depending on context. A form of Xotx2 that acts exclusively as a repressor (OtxEn‐R) was made by fusing the Xotx2 homeodomain to the Drosophila melanogaster engrailed transcriptional repressor domain. Overexpression of this protein in vivo indicates that OtxEn‐R antagonizes the activating function of endogenous Xotx2 for anterior marker genes such as XCG and goosecoid but retains the ability to repress the expression of posterior markers such as Xcad3 and Xbra. OtxEn‐R overexpression causes a severe derangement of anterior development, resulting in the loss of cement gland, eyes, stomodeal opening, and pharynx. The specification and development of anterior neural structures is dramatically abnormal up to and including the isthmic signaling center at the midbrain/hindbrain junction. This study provides good evidence that Xenopus Otx2 is required for normal head patterning and the process of anterior neural specification. We propose that a mutually antagonistic relationship between Otx and Cdx factors is a basic aspect of anteroposterior patterning in all vertebrates.
Wnt gene expression in sea urchin development: Heterochronies associated with the evolution of developmental mode
Authors: Ferkowicz Michael J. , Raff Rudolf A.
Published: March 2003

SUMMARY

The Wnt genes encode a large family of conserved secreted proteins that are widely involved in animal development. The variety and ubiquity of this ancient family suggest that Wnt genes may have been important in the evolution of animal development, including early development. To test this hypothesis, we have characterized the expression of several Wnt genes in closely related sea urchins that exhibit radically different modes of early development. Wnt‐1, ‐4, and ‐5 genes exhibit several conserved molecular and developmental characteristics, both within sea urchins and with Wnt genes examined in other animals (Ferkowicz et al. 1998). Here, we demonstrate that sea urchin Wnt‐5 transcripts are specifically detected by in situ hybridization in discrete embryonic, larval, and developing adult tissues and processes: (1) in a band of vegetal ectoderm in mesenchyme blastula stage embryos, (2) in the larval ciliary bands, (3) in tissues that form the early adult rudiment (left coelomic pouch and overlying vestibular ectoderm), and (4) in the developing adult radial nervous system. We find that the sites of Wnt‐5 transcript accumulation are conserved in species exhibiting either indirect‐ or direct‐developmental modes, suggesting that Wnt‐5 function(s) have been conserved in sea urchin development. However, dramatic heterochronic changes in Wnt‐5 gene expression have occurred in the direct‐developing species that parallel the accelerated morphological changes that occur during direct development. These results suggest that heterochronic changes in the expression of conserved developmental regulatory genes, such as the Wnt family members, are agents of evolutionary change in animal development.
Conservation of a DPP/BMP signaling pathway in the nonbilateral cnidarian Acropora millepora
Authors: Samuel Gabrielle , Miller David , Saint Robert
Published: March 2003

SUMMARY Members of the TGF‐β superfamily of signaling molecules are widespread in metazoans, but the evolutionary origin of particular subclasses of signaling mechanisms is poorly defined. The DPP/BMP class, for example, is implicated in dorsal‐ventral patterning, neural patterning, and limb development. Here we report the presence of several components of a DPP/BMP‐specific signal transduction cascade in a nonbilateral animal, the coral Acropora millepora. The discovery of these components, a putative type I receptor and two putative receptor‐activated Smads, suggests that DPP/BMP signaling predates both dorsal‐ventral pattern formation and limb development. We postulate that an ancestral role in neuroepithelial patterning may account for the high level of conservation between DPP/BMP signaling components found in this nonbilateral animal and the more complex triploblastic organisms of the arthropod and chordate phyla.
The expression of an engrailed protein during embryonic shell formation of the tusk‐shell, Antalis entalis (Mollusca, Scaphopoda)
Authors: Wanninger Andreas , Haszprunar Gerhard
Published: March 2003

SUMMARY This study presents the first detailed account of the larval and early post‐metamorphic development of a scaphopod species, Antalis entalis, since 1883. Special reference is given to the expression pattern of an engrailed protein during the formation of the embryonic (protoconch) and adult shell (teleoconch). We found that in the trochophore‐like larva the engrailed protein is expressed in shell‐secreting cells at the margin of the protoconch close to the mantle edge. During metamorphosis the growth of the protoconch and expression of the engrailed protein along its margin stop and the teleoconch starts to form. These data suggest a different genetic background regarding protoconch and teleoconch formation in the Scaphopoda and possibly all Conchifera, thus inferring a different evolutionary origin of both organs. The single anlage of the scaphopod protoconch contradicts earlier hypotheses of a monophyletic taxon Diasoma (Scaphopoda + Bivalvia), which has been mainly based on the assumption of a primarily bilobed shell in both taxa. Comparative data on engrailed expression patterns suggest nervous system patterning as the basic function of engrailed in the Bilateria. However, there are several independent gain‐of‐function events, namely segment compartmentation in the Annelida and Arthropoda, protoconch formation in the Mollusca, skeletogenesis in the Echinodermata, and limb formation in vertebrates. These findings provide further evidence that homologous genes may act in very different pathways of bilaterian body plan formation in various animal phyla.
Deuterostome evolution: early development in the enteropneust hemichordate, Ptychodera flava
Authors: Henry Jonathan Q. , Tagawa Kunifumi , Martindale Mark Q.
Published: March 2003

SUMMARY Molecular and morphological comparisons indicate that the Echinodermata and Hemichordata represent closely related sister‐phyla within the Deuterostomia. Much less is known about the development of the hemichordates compared to other deuterostomes. For the first time, cell lineage analyses have been carried out for an indirect‐developing representative of the enteropneust hemichordates, Pty‐ chodera flava. Single blastomeres were iontophoretically labeled with DiI at the 2‐ through 16‐cell stages, and their fates followed through development to the tornaria larval stage. The early cleavage pattern of P. flava is similar to that of the direct‐developing hemichordate, Saccoglossus kowalevskii, as well as that displayed by indirect‐developing echinoids. The 16‐celled embryo contains eight animal “mesomeres,” four slightly larger “macromeres,” and four somewhat smaller vegetal “micromeres.” The first cleavage plane was not found to bear one specific relationship relative to the larval dorsoventral axis. Although individual blastomeres generate discrete clones of cells, the appearance and exact locations of these clones are variable with respect to the embryonic dorsoventral and bilateral axes. The eight animal mesomeres generate anterior (animal) ectoderm of the larva, which includes the apical organ; however, contributions to the apical organ were found to be variable as only a subset of the animal blastomeres end up contributing to its formation and this varies from embryo to embryo. The macromeres generate posterior larval ectoderm, and the vegetal micromeres form all the internal, endomesodermal tissues. These blastomere contributions are similar to those found during development of the only other hemichordate studied, the direct‐developing enteropneust, S. kowalevskii. Finally, isolated blastomeres prepared at either the two‐ or the four‐cell stage are capable of forming normal‐appearing, miniature tornaria larvae. These findings indicate that the fates of these cells and embryonic dorsoventral axial properties are not committed at these early stages of development. Comparisons with the developmental programs of other deuterostome phyla allow one to speculate on the conservation of some key developmental events/mechanisms and propose basal character states shared by the ancestor of echinoderms and hemichordates.
Patterns of gene expression in the developing adult sea urchin central nervous system reveal multiple domains and deep‐seated neural pentamery
Authors: Sly Belinda J. , Hazel Jill C. , Popodi Ellen M. , Raff Rudolf A.
Published: March 2003

SUMMARY The adult sea urchin central nervous system (CNS) is composed of five radial nerve cords connected to a circular nerve ring. Although much is known about the molecular mechanisms underlying the development and function of the nervous systems of many invertebrate and vertebrate species, virtually nothing is known about these processes in echinoderms. We have isolated a set of clones from a size‐selected cDNA library prepared from the nervous system of the sea urchin Heliocidaris erythrogramma for use as probes. A total of 117 expressed sequence clones were used to search the GenBank database. Identified messages include genes that encode signaling proteins, cytoskeletal elements, cell surface proteins and receptors, cell proliferation and differentiation factors, transport and channel proteins, and a RNA DEAD box helicase. Expression was analyzed by RNA gel blot hybridization to document expression through development. Many of the genes have apparently neural limited expression and function, but some have been co‐opted into new roles, notably associated with exocytotic events at fertilization. Localization of gene expression by whole‐mount in situ hybridization shows that the morphologically simple sea urchin radial CNS exhibits complex organization into localized transcriptional domains. The transcription patterns reflect the morphological pentamery of the echinoderm CNS and provide no indication of an underlying functional bilateral symmetry in the CNS.
Why is limb regeneration possible in amphibians but not in reptiles, birds, and mammals?
Authors: Galis Frietson , Wagner Günter P. , Jockusch Elizabeth L.
Published: March 2003

SUMMARY The capacity to regenerate limbs is very high in amphibians and practically absent in other tetrapods despite the similarities in developmental pathways and ultimate morphology of tetrapod limbs. We propose that limb regeneration is only possible when the limb develops as a semiautonomous module and is not involved in interactions with transient structures. This hypothesis is based on the following two assumptions: To an important extent, limb development uses the same developmental mechanisms as normal limb development and developmental mechanisms that require interactions with transient structures cannot be recapitulated later. In amniotes limb development is early, shortly after neurulation, and requires inductive interactions with transient structures such as somites. In amphibians limb development is delayed relative to amniotes and has become decoupled from interactions with somites and other transient structures that are no longer present at this stage. The limb develops as a semi‐independent module. A comparison of the autonomy and timing of limb development in different vertebrate taxa supports our hypothesis and its assumptions. The data suggest a good correlation between self‐organizing and regenerative capacity. Furthermore, they suggest that whatever barriers amphibians overcame in the evolution of metamorphosis, they are the same barriers that need to be overcome to make limb regeneration possible in other taxa.
The Influence of Recombinant Human Erythropoietin on Tumor Necrosis Factor α and Interleukin‐10 Production by Whole Blood Cell Cultures in Hemodialysis Patients
Authors: Bryl Ewa , Myśliwska Jolanta , Dębska‐Ślizień Alicja , Rachoń Dominik , Bułło Barbara , Lizakowski Sławomir , Myśliwski Andrzej , Rutkowski Bolesław
Published: March 2003

Abstract: Impaired immunological response in hemodialysis (HD) patients, which leads to inappropriate cytokine production, is partially caused by the hyperstimulation of both T lymphocytes and monocytes/macrophages. Recent data suggest that human recombinant erythropoietin (rhEPO) may have an immunological action. The goal of our study was to estimate the influence of rhEPO treatment on the production of the inflammatory cytokine tumor necrosis factor α (TNFα) and antiinflammatory cytokin interleukin‐10 (IL‐10) in 10 HD patients receiving rhEPO for 6 months. The levels of cytokines were measured in the in vitro cultures of whole blood. The level of IL‐10 increased in all treated patients during the therapy, and it was accompanied by a transitory decrease of TNFα. The results of our studies suggest that rhEPO may reduce the inflammatory process by decreasing production of TNF α and increasing production of IL‐10.
Dose Titration Study of Tinzaparin, a Low Molecular Weight Heparin, in Patients on Chronic Hemodialysis
Authors: Egfjord Martin , Rosenlund Lene , Hedegaard Berit , Buchardt Helle Løvdahl , Stengel Christina , Gardar Petra , Andersen Lisbeth , Andersen Louise
Published: March 2003

The minimal necessary dose of Innohep (IH) (MNDI) (Innohep [tinzaparin], Leo Pharmaceutical Corp., Ballerup, Denmark) was examined in 40 patients switched from conventional heparin ([CH], Leo Pharmaceutical Corp.) to IH and in 13 patients already treated with IH. Clotting in the venous chamber and in the dialyzer was evaluated on a 4 point scale by visual inspection. IH was administrated as a bolus injection into the arterial side of the dialyzer at the beginning of dialysis sessions. The initial dose of IH was 50% of the total dose of CH used before the study (in respective IU). According to clotting in the venous chamber or dialyzer, the dose of IH was titrated by stepwise changes of 500 IU to the lowest possible dose until 3 subsequent dialysis sessions without clotting were obtained. The total dose of CH (bolus and infusion) before switching was 6,162 ± 2,100 IU. The bleeding time from the cannulation site after dialysis, in 24 patients with A‐V fistulas, was 7.1 ± 2.8 min(triplicates). Eight patients were excluded before achieving the MNDI, 3 due to bleeding not clearly related to heparinization (1 due to gingival bleeding, 1 to epistaxis, and 1 to sugillations), 1 due to alopecia, 2 due to a need of more than 10,000 IU of IH, and 2 patients due to cessation of treatment resulting from anxiety. After switching over, the MNDI amounted to 66 ± 26% in respective IU. The conversion IH/CH ratio correlated significantly to the blood flow rate and the type of dialyzer. When compared on 3 subsequent sessions before and after switching to IH, no differences were found in the bleeding time after decannulation and in clotting in the venous chamber while dialyzer clotting fell on the visual scale from an average of 0.36 to 0.19 (p < 0.01). No total clot formation was observed during the study. The MNDI correlated positively to the body weight, blood flow rate, and time on dialysis (with the respective coefficients of correlation of r being 0.58, 0.44, and 0.30, p < 0.05) and was also influenced by the type of dialyzer. The average MNDIs for the Hemoflow‐FS hollow‐fiber (Fresenius, Bad Homburg, Germany), Lundia PRO plate (Gambro, Lund, Sweden), and Polyflux hollow fiber (Gambro) were 2,571, 3,727, and 5,020 IU (p < 0.01, ANOVA). In patients on chronic hemodialysis, IH given as a bolus of 4,250 IU effectively prevented extracorporeal clotting during dialysis, similarly to CH. However, a considerable individual variation in MNDIs not related to the need for CH was observed, and this necessitates individual dosage adjustments to obtain the optimal prevention of clotting with minimal bleeding risk.
Dialysate Pressure Isobars in a Hollow‐Fiber Dialyzer Determined from Magnetic Resonance Imaging and Numerical Simulation of Dialysate Flow
Authors: Osuga Toshiaki , Obata Takayuki , Ikehira Hiroo , Tanada Shuji , Sasaki Yasuhito , Naito Hidemune
Published: March 2003

A procedure to determine dialysate pressure isobars by comparing the results of magnetic resonance imaging (MRI) and numerical simulation of the dialysate flow was established. The assumption used in the filtration analyses, that the dialysate pressure varies only in the central‐axial direction, is supported by the finding that the determined isobars have no steep radial gradient. MRI of the contrast solution permeating the hollow fibers verifies the uniformity of the hollow fiber density in the dialyzer.
Clinical Implications of Blood Substitutes
Authors: Gerson Greenburg
Published: March 2003

Red cell substitutes are developing rapidly and progressing in their clinical testing. The original concept of a shelf storable oxygen carrying solution for use in trauma and other emergency situations still remains valid. Of interest is the potential for red cell substitutes to be used in other areas of surgery, traditionally the realm of autologous transfusion. This article describes some of the logic behind defining which areas of application are potentially useful in the surgical arena.
The Acute Effect of Intravenously Administered Recombinant Human Erythropoietin on the Immune Response of Uremic Patients Maintained on Regular Hemodialysis
Authors: William  , Saad  , Salib  , Riad  , Mahran  , Iskander  , Cozma  , Barsoum
Published: March 2003

The uremic patient on regular hemodialysis (RHD) is subjected to a wide range of immune modulators including the uremic state per se, multiple transfusions and exposure to bioincompatible materials and endotoxins. Erythropoietin (EPO) therapy may raise concern about its potential influence on this complex scenario. To envisage this issue, 15 adequately selected patients, stable on RHD, were randomly assigned in a 2:1 ratio into EPO and placebo groups. After initial assessment and determination of baseline values, they received, in a double‐blind manner, either EPO or normal saline as an intravenous bolus immediately after termination of dialysis for 30 successive sessions. Thirty minutes later, following sessions 1, 10, 20, and 30, samples were obtained for determination of blood counts, red cell indices, peripheral lymphocyte counts (PLC), CD4/CD8 ratios, blood EPO levels, and serum concentrations of interleukins (IL) IL‐2r, IL‐3, and IL‐6, tumor necrosis factor (TNFs and TNFα), and neopterin (NPT). Blood EPO levels displayed the predicted rise in the EPO group, which correlated with partial improvement of red cell parameters. The mean total leukocyte count and PLCs was significantly increased in the EPO group (p < 0.05) but not in the placebo group. CD4/CD8 ratios were not significantly changed in either group. The serum concentrations of IL‐2r, IL‐3, and NPT remained fairly stable while that of IL‐6 was widely variable in both study groups. The mean serum concentrations of TNF and particularly TNFα showed a steady and statistically significant increment in the EPO group from 6 to 41 pg/ml (p < 0.05) and 93 to 128 pg/ml (p < 0.03), respectively. No significant change was noticed in the control group. It is concluded that intravenous administration of EPO under the conditions of this study may have an immune stimulating effect. This is shown by the release of TNFs, which in turn may be responsible, through different potential mechanisms, for the increase in the mean peripheral neutrophil count and the blunting of erythroid responsiveness to EPO therapy.