bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pepsinogen Releasing Effect of Helicobacter pylori Lipopolysaccharide
Authors: Young G. O. , Brown S. , Stemmet N. , Lastovica A. J. , Marks I. N. , Modlin I. M. , Kidd M.
Published: March 2003

Background. Helicobacter pylori lipopolysaccharide (LPS) affects pepsinogen release by a nontoxic mechanism. We hypothesized that this effect was characteristic of the organism and related to the clinical status of the strain.

Materials and methods. LPS was isolated from 11 H. pylori strains whose pathogenic profile was known and four other nongastric bacteria. The effects of luminal LPS on guinea pig gastric mucosal pepsinogen release was evaluated using the Ussing chamber technique. CCK‐8 (10−9M) was used as a positive control.

Results. H. pylori LPS dose‐dependently stimulated pepsinogen release with a maximal stimulation at 250 µg/ml (~4500%; p < .001 vs. control). LPS from other Helicobacter or Campylobacter species had no effect on pepsinogen release. ANOVA demonstrated significant differences in the efficacies of pepsinogen release between the 11 clinical H. pylori strains (p < .0001) despite the fact that they were all cagA+ and 90% had the cytotoxic vacA subtype s1. Physical and chemical disruption of the LPS suggested that both the structure and the carbohydrate composition of this molecule may play a critical role in pepsinogen release. Polymyxin B partly (p < .03) inhibited and dephosphorylation completely inhibited (p = .0002) LPS‐stimulated pepsinogen release.

Conclusion. Pepsinogen release is an innate property of all cagA+H. pylori LPS. The structure of the molecule and composition of side‐chains are important in this response which appears to be partially lipid A driven.
Polaprezinc Attenuates Helicobacter pylori‐Associated Gastritis in Mongolian Gerbils
Authors: Ishihara Ryu , Iishi Hiroyasu , Sakai Noriko , Yano Hiroyuki , Uedo Noriya , Narahara Hiroyuki , Iseki Kazushige , Mikuni Tomiko , Ishiguro Shingo , Tatsuta Masaharu
Published: March 2003

Background. The ammonia‐monochloramine system plays an important role in Helicobacter pylori‐associated gastric mucosal injury. Polaprezinc, a new antiulcer agent, has a scavenging action against monochloramine. The aim of the experiment was to investigate the inhibitory effects of polaprezinc on the H. pylori‐induced gastritis in Mongolian gerbils.

Materials and Methods. Mongolian gerbils fasting for 24 hours were orally given culture broth containing 2–4 × 108 colony‐forming units of H. pylori ATCC 43054 per milliliter. From 4 hours after inoculation until the end of the experiment, gerbils were given chow pellets with or without 0.02% polaprezinc. All gerbils were killed 12 weeks later. The grades of H. pylori density and histologic features of gastritis were evaluated in accordance with the Updated Sydney System. The scavenging effect of polaprezinc on monochloramine was investigated spectrophotometrically.

Results. Polaprezinc had little or no influence on the H. pylori density in both pyloric and fundic mucosae. However, it significantly attenuated the development of polymorphonuclear neutrophil activity, mononuclear infiltration, and surface epithelial erosion in both pyloric and fundic mucosae compared with those of the control group. H. pylori inoculation significantly increased the heights of both pyloric and fundic mucosae (mainly due to the increased height of foveolar hyperplasia), but polaprezinc inhibited the increase of mucosal thickness in both pyloric and fundic mucasae. No intestinal metaplasia was detected in this study. Spectrophotometric examination revealed that polaprezinc scavenged monochloramine.

Conclusions. Polaprezinc inhibited the development of H. pylori‐induced gastritis through its scavenging action against monochloramine.
Enterocromaffin‐Like Cell Tumor Induced by Helicobacter pylori Infection in Mongolian Gerbils
Authors: Kagawa Jiro , Honda Shoji , Kodama Masaaki , Sato Ryugo , Murakami Kazunari , Fujioka Toshio
Published: March 2003

Background. Gastric carcinoids are strongly associated with chronic atrophic gastritis A, and it is suggested that hypergastrinemia plays a critical role in development of gastric carcinoids. Since Helicobacter pylori infection causes hypergastrinemia, it is held that H. pylori infection produces gastric carcinoids. We followed the histological changes of H. pylori‐infected stomachs of Mongolian gerbils for a long time.

Materials and Methods. Five‐week‐old‐male Mongolian gerbils were infected with H. pylori ATCC 43504 with cagA gene, expressing vacuolating cytotoxin. Determination of the serum gastrin and histopathological examination of the stomach at 6, 12, 18, and 24 months after H. pylori inoculation was studied and compared with uninfected animals.

Results In infected animals, the gastric carcinomas appeared 18 and 24 months after infection. Endocrine cell dysplasias and carcinoids with marked atrophic gastritis of the oxyntic mucosa were observed in the infected animals 24 months after H. pylori inoculation. The serum gastrin level in the infected group increased from an average of 86.2 pg/ml at the beginning of the study to an average of 498 pg/ml and 989 pg/ml at 18 and 24 months after infection, respectively. These changes in the serum gastrin levels were significant compared with uninfected controls that showed no changes.

Conclusions. H. pylori infection caused not only gastric carcinomas but also enterochromaffin‐like cell tumors in Mongolian gerbils, due to hypergastrinemia. This model is thought to be useful to study the relationship between hypergastrinemia and gastric carcinoids.
Statistical Model of the Interactions Between Helicobacter pylori Infection and Gastric Cancer Development
Authors: Welin Martin , Holmgren Noél M. A. , Nilsson Patric , Enroth Helena
Published: March 2003

Background. The bacterium Helicobacter pylori is associated with a number of gastrointestinal diseases, such as gastric ulcer, duodenal ulcer and gastric cancer. Several histological changes may be observed during the course of infection; some may influence the progression towards cancer. The aim of this study was to build a statistical model to discover direct interactions between H. pylori and different precancerous changes of the gastric mucosa, and in what order and to what degree those may influence the development of the intestinal type of gastric cancer.

Methods. To find direct and indirect interactions between H. pylori and different histological variables, log‐linear analyses were used on a case–control study. To generate mathematically and biologically relevant statistical models, a designed algorithm and observed frequency tables were used.

Results. The results show that patients with H. pylori infection need to present with proliferation and intestinal metaplasia to develop gastric cancer of the intestinal type. Proliferation and intestinal metaplasia interacted with the variables atrophy and foveolar hyperplasia. Intestinal metaplasia was the only variable with direct interaction with gastric cancer. Gender had no effect on the variables examined.

Conclusion. The direct interactions observed in the final statistical model between H. pylori, changes of the mucosa and gastric cancer strengthens and supports previous theories about the progression towards gastric cancer. The results suggest that gastric cancer of the intestinal type may develop from H. pylori infection, proliferation and intestinal metaplasia, while atrophy and foveolar hyperplasia interplay with the other histological variables in the disease process.
Helicobacter pylori Infection, Mucosal Atrophy and Intestinal Metaplasia in Asian Populations: A Comparative Study in Age‐, Gender‐ and Endoscopic Diagnosis‐Matched Subjects
Authors: Matsuhisa Takeshi M. , Yamada Nobutaka Y. , Kato Shunji K. , Matsukura Norio M.
Published: March 2003

Background. It is known that the incidence and mortality rate of gastric cancer is high among Japanese and Chinese populations, but extremely low in Thai and Vietnamese populations. The aim of this study was to investigate the prevalence of Helicobacter pylori infection and the differences in the glandular atrophy and intestinal metaplasia scores in stomach specimens of Asian adult subjects of different races.

Materials and Methods. Chinese, Thai, Vietnamese and Japanese patients were matched by age, gender and endoscopic diagnosis, in order to compare the differences in incidence of H. pylori‐related peptic ulcer disease and the prevalence of H. pylori infection among four Asian populations (n = 700). Glandular atrophy scores and intestinal metaplasia scores were also compared among four Asian populations divided into H. pylori‐positive cases (n = 120, 109, 145, 80, respectively) and H. pylori‐negative cases (n = 55, 66, 30, 95, respectively).

Results. Among peptic ulcers, gastric ulcer was more frequently seen in Japanese subjects than in the other Asian populations examined. On the other hand, duodenal ulcer was more frequently seen in other Asian populations than in Japanese subjects. The prevalence of H. pylori infection was similar in the Japanese (Tokyo) and Chinese (Beijing and Fuzhou) populations. It was higher in Thai (Chiang Mai) subjects compared with Japanese subjects. On the other hand, Vietnamese (Ho Chi Minh) subjects had significantly lower rates of H. pylori infection than Japanese subjects. The glandular atrophy and intestinal metaplasia scores in the stomach were significantly higher in the H. pylori‐positive Japanese subjects than in H. pylori‐positive subjects belonging to other Asian populations, except for the higher glandular atrophy scores in Chinese rather than Japanese subjects. On the other hand, there were no significant differences in the glandular atrophy and intestinal metaplasia scores in the angulus of the stomach among H. pylori‐negative subjects belonging to the different Asian populations examined.

Conclusions. Gastric ulcer was more common among Japanese subjects, while duodenal ulcer was more common among the other Asian populations examined. Japanese subjects with H. pylori infection showed more severe atrophic and metaplastic gastritis compared with that in other Asian subjects with H. pylori infection. These results may be related to the higher incidence of gastric cancer noted in Japanese subjects and the lower incidence of the cancer seen in Thai and Vietnamese patients.
p16Ink4a is Overexpressed in H. pylori‐Associated Gastritis and is Correlated with Increased Epithelial Apoptosis
Authors: Shirin Haim , Hibshoosh Hanina , Kawabata Yuichi , Weinstein I. Bernard , Moss Steven F
Published: March 2003

Background. Cell cycle regulatory proteins may be critical targets during carcinogenesis. We have previously shown that chronic H. pylori infection is associated with decreased expression of the cyclin dependent kinase inhibitor (CDI) p27kip1. Loss of p27kip1 and p16Ink4a (p16) expression, another CDI, has been reported during the progression of gastric tubular adenomas to advanced gastric cancer. The aim of the current study was to examine whether H. pylori infection also affects the expression of p16 in the gastric mucosa of H. pylori‐infected patients.

Methods. p16 expression was evaluated in gastric antral biopsies by immunohistochemistry in 50 patients with nonulcer dyspepsia (n = 18 uninfected, n = 32 H. pylori infected, 24 by cagA+ strains). Adjacent sections were stained for proliferating epithelial cells (by Ki67) and for apoptotic cells (by TUNEL assay).

Results. Both in H. pylori infected and uninfected patients the expression of p16 was higher in the neck and base of the gland than in the foveolar region. Epithelial staining for p16 was increased with H. pylori infection (31.3% vs. 11.1% in the foveolar region, 68.8% vs. 27.8% in the neck and 75% vs. 50% in the glandular base). There was no correlation between the expression of 16 and proliferation but there was a significant positive correlation between apoptosis and 16 immunostaining.

Conclusions. The tumor suppressor gene 16 is over expressed in gastric epithelial cells of H. pylori infected patients and this is associated with an increase in apoptosis. These findings suggest a possible role for this cell cycle regulator in the increase in gastric cell turnover that is associated with H. pylori infection.
Success of the State Pain Initiatives
Authors: Dahl June L. , Bennett Mary E. , Bromley Matthew D. , Joranson David E.
Published: March 2003

purpose: The purpose of this article is to describe the history of the State Cancer Pain Initiative (CPI) movement and current initiative activities that are directed at improving the management of cancer pain.

overview: The undertreatment of pain is a major public health problem in the United States. State CPIs strive to remove the barriers to effective cancer pain management through the provision of innovative professional, patient, and public educational programs, through institutional change projects, and through public advocacy. Collaboration with organizations that share common goals is important in sustaining and maximizing the impact of the movement.

clinical implications: Professionals, patients, and families benefit from the work of the State Initiatives. By enhancing the knowledge and skills of clinicians, supporting institutional change, and teaching patients and families the importance of effective pain control, the Initiatives help to improve the quality of life for all cancer survivors. Models of intervention that respond to local needs are discussed, and legislative and advocacy efforts that affect care also are noted.
Ensuring A Good Death
Authors: Lynch Maureen , Abrahm Janet
Published: March 2003

purpose: The purpose of this article is to describe how the commitment of the Dana‐Farber Cancer Institute to pain management, quality of life, and optimal end‐of‐life care is operationalized through a comprehensive pain and palliative‐care program.

overview: Institutional standards for pain management often address only the physical aspects of pain. Effective pain management requires assessment and interventions that address the multidimensional nature of pain, suffering, and quality of life throughout the cancer continuum. This approach seeks to lay the foundation of comfort and peace associated with a good death.

clinical implications: Institutional pain management standards need to reflect the complexity of pain, especially cancer‐related pain, by emphasizing comprehensive, holistic assessment and multimodality approaches to pain control and quality‐of‐life issues.
Leptomeningeal Involvement in Chronic Lymphocytic Leukemia
Authors: Morrison Candis , Shah Surendra , Flinn Ian W.
Published: March 2003

purpose
: This review and case report address the rare complication of leptomeningeal involvement in patients with chronic lymphocytic leukemia.

overview
: Chronic lymphocytic leukemia is the most common form of leukemia, with more than 200,000 cases reported in the past 20 years. An uncommon complication of the disorder is central nervous system invasion. To date, only 21 cases have been reported, and their presenting symptoms have been heterogeneous and often nonspecific, including headache, cranial nerve abnormalities, confusion, ataxia, nausea, vomiting, and fever. The diagnosis is confirmed by the presence of a clonal population of lymphocytes in the cerebrospinal fluid. Treatment is either intrathecal or intraventricular chemotherapy with adjuvant radiation therapy or radiation alone. Prognosis is improved by prompt and aggressive therapy. In this case report, a 61‐year‐old man developed severe ataxia, vertigo, and occipital headaches 4 weeks after diagnosis with otherwise asymptomatic chronic lymphocytic leukemia. After treatment with both radiation to the head and neck and intrathecal methotrexate the patient achieved complete symptom resolution. Thus far, no additional systemic cytotoxic chemotherapy has been necessary.

clinical implications
: Because central nervous system invasion is uncommon in chronic lymphocytic leukemia, it may go undiagnosed and under‐reported. Providers of patients with this disease need to be aware of possible central nervous system invasion when patients present with cranial nerve signs or symptoms and/or nonspecific neurologic manifestations. Early identification and prompt central nervous system‐directed chemotherapy can affect morbidity and quality of life positively.
Partner Abandonment of Women with Breast Cancer: Myth or Reality?
Authors: Taylor‐Brown Jill , Kilpatrick Marilyn , Maunsell Elizabeth , Dorval Michel
Published: March 2003

Purpose: The purpose of this article is to determine the existing evidence related to marital breakdown after a breast cancer diagnosis by reviewing studies that highlight two current belief models: the lay belief model and the clinical belief model.

Overview: The small number of studies conducted on this topic since 1988 revealed no data to confirm the lay belief model, which proposes that women with breast cancer are abandoned by their partners. The evidence appears to support the clinical belief model that the majority of marital relationships remain stable after breast cancer and that breakdown is most likely in those relationships with pre‐existing difficulties.

Clinical implications: This review indicates that it may be important for clinicians to routinely ask about the quality of the marital relationship as part of the initial assessment, because it appears that this may be a main predictor of post‐diagnosis marital adjustment. In addition, greater dissemination of the findings of this review through the media and through cancer organizations is needed to more accurately reflect the experience of couples facing breast cancer and, thus, to begin to change the public perception of partner desertion after breast cancer. This could help both women with breast cancer and women from the general population who may one day confront a breast cancer diagnosis.
Problem‐Solving Cancer Care Education for Patients and Caregivers
Authors: Bucher Julia A. , Loscalzo Matthew , Zabora James , Houts Peter S. , Hooker Craig , BrintzenhofeSzoc Karlynn
Published: March 2003

Purpose: A program evaluation was conducted to explore the potential effects of a 90‐minute problem‐solving education session for persons with advanced cancer and their families.

Description of program: Patients with advanced cancer and their families, who were visiting a tertiary‐care outpatient setting, were invited to attend a 90‐minute individualized educational session that taught basic problem‐solving principles using a cognitive‐behavioral framework. Pre‐education and posteducation data were collected about the confidence of participants in providing care, their feelings about being informed about resources, and their perceptions of their problem‐solving ability.

Results: At baseline, most participants reported low confidence about their ability to provide cancer care and felt uninformed about community resources, but they viewed themselves as moderate‐to‐good problem solvers. Forty‐two educational sessions were delivered to 49 caregivers and 40 patients. Two months later, participants reported feeling more informed about community resources and achieved higher posteducation scores for problem‐solving ability. More caregivers than patients reported that reading The Home Care Guide for Cancer made a great deal of difference in their approach to home care.

Clinical implications: Most educational sessions for families affected by cancer focus on delivering information, not on building skills. These findings suggest that a one‐on‐one educational session that teaches problem‐solving skills can be successfully delivered in a busy clinic setting. Family caregivers are especially likely to benefit from this program.
Educating Patients on Sentinel Lymph Node Dissection for Breast Cancer
Authors: Swenson Karen K. , Sladek Mary L. , Lally Robin M. , Tuttle Todd M.
Published: March 2003

Purpose: This article reviews the current literature on lymphatic mapping and sentinel lymph node dissection (SLND) for breast cancer and presents educational information for patients who are considering undergoing this procedure.

Overview: Lymphatic mapping with SLND has been tested widely in patients with breast cancer, primarily in the context of clinical trials. Research studies have found a high degree of accuracy, with the sentinel lymph node (SLN) predicting the status of the axillary node basin. The ability of the surgeon to identify the SLN and the accuracy of the technique correlate with the number of procedures conducted. With the increase in the number of patients having lymphatic mapping and SLND for breast cancer who may not be part of a clinical trial, there is a need for educational materials to help clinicians teach patients about the procedure.

Clinical implications: Because of the complexity of the information, patients need both written and verbal information to decide whether to undergo an SLND. In the setting of a clinical trial, patient education materials add to the informed consent document. As the use of SLND for breast cancer becomes more common, the need for clear, concise, informative patient education materials is even more imperative.
Axial variation in the threespine stickleback: genetic and environmental factors
Authors: Ahn Dae‐gwon , Gibson Greg
Published: March 2003

Subtle differences in the pattern of arrangement of types of vertebrae and associated median skeletal structures between a benthic and limnetic species pair of threespine stickleback from Paxton Lake, British Columbia, are typical of those found throughout the range of theGasterosteus aculeatusspecies complex. We established laboratory colonies from just three individuals of each species, and studied the effect of three generations of inbreeding on axial morphology. There was sufficient divergence in the location of individual elements between families to regenerate close to the entire range of axial diversity seen in threespine sticklebacks worldwide. Analysis of the patterns of variance and covariance between the axial locations of elements provides evidence for the action of both meristic and homeotic processes in the generation of morphological divergence within each species. Hybrid sticklebacks produced by the cross of limnetic and benthic parents tend to have intermediate morphologies, with dominance of either parental type evident for some elements. Effects of temperature and salinity were found to be small in direct comparison with between‐family effects, and varied according to genetic background. These results demonstrate that considerable genetic variation for axial morphology is maintained in natural populations of threespine stickleback, and that differences between populations may be brought about rapidly by changes in frequency of alleles that have coordinated effects along the body axis.
Phenotypic and dynamical transitions in model genetic networks I. Emergence of patterns and genotype‐phenotype relationships
Authors: Salazar‐Ciudad I. , Newman S. A. , Solé R. V.
Published: March 2003

SUMMARY Genotype–phenotype interactions during the evolution of form in multicellular organisms is a complex problem but one that can be aided by computational approaches. We present here a framework within which developmental patterns and their underlying genetic networks can be simulated. Gene networks were chosen to reflect realistic regulatory circuits, including positive and negative feedback control, and the exchange of a subset of gene products between cells, or within a syncytium. Some of these networks generate stable spatial patterns of a subset of their molecular constituents, and can be assigned to categories (e.g., “emergent” or “hierarchic”) based on the topology of molecular circuitry. These categories roughly correspond to what has been discussed in the literature as “self‐organizing” and “programmed” processes of development. The capability of such networks to form patterns of repeating stripes was studied in network ensembles in which parameters of gene‐gene interaction were caused to vary in a manner analogous to genetic mutation. The evolution under mutational change of individual representative networks of each category was also simulated. We have found that patterns with few stripes (≤3) are most likely to originate in the form of a hierarchic network, whereas those with greater numbers of stripes (≥4) originate most readily as emergent networks. However, regardless of how many stripes it contains, once a pattern is established, there appears to be an evolutionary tendency for emergent mechanisms to be replaced by hierarchic mechanisms. These results have potential significance for the understanding of genotype‐phenotype relationships in the evolution of metazoan form.
AmphiFoxE4, an amphioxus winged helix/forkhead gene encoding a protein closely related to vertebrate thyroid transcription factor‐2: expression during pharyngeal development
Authors: Yu Jr‐Kai , Holland Linda Z. , Jamrich Milan , Blitz Ira L. , Holland Nicholas D.
Published: March 2003

SUMMARYThe full‐length sequence and developmental expression of amphioxusAmphiFoxE4are described. Transcripts of the gene are first detected in the pharyngeal endoderm, where the club‐shaped gland is forming and sub‐sequently in the definitive gland itself.AmphiFoxE4is closely related to vertebrate genes encoding the thyroid‐specific transcription factor‐2 (TTF2), which plays an early developmental role in the morphogenesis of the thyroid gland and a later role in hormone‐mediated control of thyroid function. In amphioxus,AmphiFoxE4expression is not thyroid specific because the club‐shaped gland, the only structure expressing the gene, is not homologous to the vertebrate thyroid; instead, the thyroid homologue of amphioxus is a specialized region of the pharyngeal endoderm called the endostyle. We propose that (a) the pharynx of an amphioxus‐like ancestor of the vertebrates included a club‐shaped gland that expressedFoxE4as well as an endostyle that did not, and (b) the club‐shaped gland soon disappeared in the vertebrate line of descent but (c) not before there was a homeogenetic transfer ofFoxE4expression from the club‐shaped gland to the nearby endostyle. Such a transfer could have provided part of the genetic program enabling the endostyle to separate from the pharyngeal endoderm and migrate away as the rudiment of the thyroid gland.
Evolution of discrete Notch‐like receptors from a distant gene duplication in Caenorhabditis
Authors: Rudel David , Kimble Judith
Published: March 2003

SUMMARY Caenorhabditis elegans possesses two Notch‐like receptors, LIN‐12 and GLP‐1, which have both overlapping and individual biological functions. We examined the lin‐12 and glp‐1 genes in closely related nematodes to learn about their evolution. Here we report molecular and functional analyses of lin‐12 orthologs from two related nematodes, C. briggsae (Cb) and C. remanei (Cr). In addition, we compare these lin‐12 findings with similar studies of Cb‐glp‐1 and Cr‐glp‐1 orthologs. Cb‐LIN‐12 and Cr‐LIN‐12 retain the same number and order of motifs as Ce‐LIN‐12. Intriguingly, we find that LIN‐12 conservation differs from that of GLP‐1 in two respects. First, individual motifs are conserved to a different degree for the two receptors. For example, the transmembrane domain is 16–32% identical among LIN‐12 orthologs but 65–70% identical among GLP‐1 orthologs. Second, certain amino acids are conserved in a receptor‐specific manner, a phenomenon most prevalent in the CC‐linker. We suggest that LIN‐12 and GLP‐1 have been molded by selective constraints that are receptor specific and that the two proteins may not be entirely interchangeable. To analyze the functions of the lin‐12 orthologs, we used RNA‐mediated interference (RNAi). Cb‐lin‐12(RNAi) or Cr‐lin‐12(RNAi) progeny are nearly 100% Lag, a larval lethality typical of C. elegans lin‐12 glp‐1 double mutants, but not the primary defect observed in Ce‐lin‐12 null mutants or Ce‐lin‐12(RNAi). Therefore, LIN‐12 functions are similar, but not identical, among the Caenorhabditis species. We suggest that ancestral functions may have been divided between LIN‐12 and GLP‐1 receptors in a process contributing to the retention of both genes after gene duplication (i.e., subfunctionalization).
Development and evolution of adaptive polyphenisms
Authors: Nijhout H. Frederik
Published: March 2003

SUMMARYPhenotypic plasticity is the primitive character state for most if not all traits. Insofar as developmental and physiological processes obey the laws of chemistry and physics, they will be sensitive to such environmental variables as temperature, nutrient supply, ionic environment, and the availability of various macro‐ and micronutrients. Depending on the effect this phenotypic plasticity has on fitness, evolution may proceed to select either for mechanisms that buffer or canalize the phenotype against relevant environmental variation or for a modified plastic response in which some ranges of the phenotypic variation are adaptive to particular environments. Phenotypic plasticity can be continuous, in which case it is called a reaction norm, or discontinuous, in which case it is called a polyphenism. Although the morphological discontinuity of some polyphenisms is produced by discrete developmental switches, most polyphenisms are due to discontinuities in the environment that induce only portions of what is in reality a continuous reaction norm. In insect polyphenisms, the environmental variable that induces the alternative phenotype is a token stimulus that serves as a predictor of, but is not itself, the environment to which the polyphenism is an adaptation. In all cases studied so far, the environmental stimulus alters the endocrine mechanism of metamorphosis by altering either the pattern of hormone secretion or the pattern of hormone sensitivity in different tissues. Such changes in the patterns of endocrine interactions result in the execution of alternative developmental pathways. The spatial and temporal compartmentalization of endocrine interactions has produced a developmental mechanism that enables substantial localized changes in morphology that remain well integrated into the structure and function of the organism.
Sex determination: where environment and genetics meet
Authors: Crews David
Published: March 2003

SUMMARYIn mammals and birds the genetic constitution established at the time of fertilization determines the type of gonad that develops, whereas in all crocodilians and many turtles it is the temperature experienced during the mid‐trimester of embryogenesis that initiates gonadal differentiation. Research with the red‐eared slider suggests considerable conservation in the genetic cascades that underlie the sex determination process in vertebrates and, further, that the patterns of expression of these genes appear to reflect phylogenetic relationships, with turtles being more similar to mammals than they are to birds and crocodilians. After the determination and differentiation of an individual's gonadal sex, epigenetic forces shape those morphological, physiological, and behavioral traits that characterize each individual's unique sexuality. Research with the leopard gecko thus relates to the fundamental question of what factors determine individual variability, particularly as it relates to sexually dimorphic behaviors. Taken together, this research illustrates how sexuality depends on sex, but sex should not be confused with sexuality. That is, sex is merely a means of categorizing individuals or gonads, whereas sexuality serves as a descriptor of concordant traits each of which is typically sexually dimorphic in its expression.
Mutants highlight the modular control of butterfly eyespot patterns
Authors: Monteiro Antónia , Prijs Joop , Bax Minka , Hakkaart Thomas , Brakefield Paul M.
Published: March 2003

SUMMARY The eyespots on butterfly wings are thought to be serially homologous pattern elements. Yet eyespots differ greatly in number, shape, color, and size, within and among species. To what extent do these serially homologues have separate developmental identities, upon which selection acts to create diversity? We examined x‐ray–induced mutations for the eyespots of the nymphalid butterfly Bicyclus anynana that highlight the modular control of these serially homologous wing pattern elements. These mutations reduce or eliminate individual eyespots, or groups of eyespots, with no further effect on the wing color pattern. The collection of mutants highlights a greater potential developmental repertoire than that observed across the genus Bicyclus. We studied in detail one such mutation, of codominant effect, that causes the elimination of two adjacent eyespots on the ventral hindwing. By analyzing the expression of genes known to be involved in eyespot formation, we found an alteration in the differentiation of the “organizing” cells at the eyespot's center. No such cells differentiate in the wing subdivisions lacking the two eyespots in the mutants. We propose several developmental models, based on wing compartmentalization in Drosophila, that provide the first framework for thinking about the molecular evolution of butterfly wing pattern modularity.
Effect of Drug‐Polymer Interaction on the Release Characteristics of Methacrylic Acid Copolymer Microcapsules Containing Theophylline
Authors: Hsiue Ging‐Ho , Liao Chao‐Ming , Lin Shan‐Yang
Published: March 2003

Theophylline anhydrate microcapsules with different amounts of MA/MMA copolymer (Eudragit L) were prepared by the solvent evaporation method. Qualitative as well as quantitative investigation of the drug‐polymer interaction by Fourier transform infrared (FTIR) spectroscopy with a curve fitting program was undertaken. The release mechanisms of theophylline in pH 1.2 and pH 6.8 media were also studied to elucidate the effect of drug‐polymer interaction on the release characteristics of microcapsules. Direct evidence for a hydrogen bonding interaction between theophylline and Eudragit L in microcapsules was obtained. Moreover, the fraction of hydrogen bonded theophylline increased with the increase of Eudragit L. The dissolution of theophylline from microcapsules exhibited an enteric‐coated release property. The drug release mechanism was found to fit the Higuchi matrix model in the simulated gastric acid condition, but drug release was much more rapid in the pH 6.8 buffer solution. The drug release rate decreased as the composition of theophylline increased, and it was proportional to the fraction of hydrogen bonded theophylline. These results suggest that the increased fraction of hydrogen bonded theophylline in microencapsulation might improve the mixing and dispersibility of theophylline in the Eudragit L matrix, thus resulting in the increase of the release rate of theophylline from microcapsules.
Serum Amyloid A and P Protein Levels are Lowered by Dextran Sulfate Cellulose Low‐Density Lipoprotein Apheresis
Authors: Yoshidome Hiroaki , Kuriyama Masaru , Fujiyama Jiro , Osame Mitsuhiro
Published: March 2003

The present study describes the short‐term effect of dextran sulfate cellulose (DSC) low‐density lipoprotein (LDL) apheresis using a plasma separator equipped with a polysulfone (PS) membrane filter (PS/DSC‐LDL apheresis) on the serum amyloid A (SAA) and P (SAP) protein levels during treatment in a patient with familial hypercholesterolemia (type IIa, heterozygote). PS/DSC‐LDL apheresis markedly lowered both the SAA (reduction percentage, 84.1 ± 8.2%) and SAP (91.4 ± 5%) levels, which returned to their respective initial levels within 4 days. Experimentally, the levels of both proteins also decreased on passage through the DSC minicolumn without a PS membrane, indicating that the DSC resin had an affinity to both proteins. These results suggest that PS/DSC‐LDL apheresis may be advantageous for amyloid protein accumulating disorders, including amyloidosis and atherosclerosis.
A Novel Technique for Cardiopulmonary Bypass Using Vacuum System for Venous Drainage with Pressure Relief Valve: An Experimental Study
Authors: Taketani Satoshi , Sawa Yoshiki , Masai Takafumi , Ichikawa Hajime , Kagisaki Koji , Yamaguchi Takahiro , Ohtake Sigeaki , Matsud Hikaru
Published: March 2003

To decrease the circuit priming volume, develop safety, and simplify the equipment, a cardiopulmonary bypass (CPB) circuit using a vacuum suction venous drainage system with a pressure relief valve was developed. The efficacy of this vacuum system was compared to that of a conventional siphon system. The system contains a powerful vacuum generator and a pressure relief valve to keep the negative pressure constant when blood suction is used. Using 8 mongrel dogs, the feasibility and the efficacy of this CPB system was tested. The changes in the negative pressure in the reservoir were within 5 mm Hg whether the suction lines were switched on or off. In all animals the amount of blood in the venous reservoir was stable throughout bypass. The decrease of priming volume was from 725 ml (siphon system) to 250 ml (vacuum system). At the end of CPB, the levels of hemoglobin in the vacuum system were significantly higher than those in the siphon system. These results demonstrated that this vacuum drainage system can provide simplification and a miniaturization of the cardiopulmonary bypass circuit resulting in low hemodilution during CPB.
Plasmapheresis in Treatment of Acute Oligoanuria in Crescentic Glomerulonephritis
Authors: Grcˇevska  , Polenaković  , Stojkovski Lj. , Polenaković
Published: March 2003

Plasmapheresis therapy can provide an approach in the treatment of crescentic glomerulonephritis by mechanically removing nephritogenic factors from the circulation, both antiglomerular basement membrane antibodies and circulating immune complexes as well as antineutrophil cytoplasmic antibodies (ANCAs). We present our experience with plasmapheresis treatment in patients with acute oligoanuria caused by crescentic glomerulonephritis. We used membrane plasmapheresis to treat 11 patients with crescentic glomerulonephritis with more than 80% crescent formation on biopsy and with acute onset of the disease and acute oligoanuria. The immune complex form of the disease was documented in 7, the anti‐glomerular basement membrane antibodies mediated (anti‐GBM) form in 2, the ANCA‐associated form in 1 case, and the recurrent anti‐GBM form in 1 patient. Plasmapheresis was performed 2–3 times weekly using Bellco BL 500 and Gambro 2000 PF plasma filters. The total number of plasma exchanges (2,000–2,200 ml each) for each patient was 5–9. The treatment was associated with steroids and cyclophosphamide. The improvement of renal function with the start of diuresis and significant decrease of creatinine from the range of 786–1,301 μM at the start of the treatment was noted in 5 of the 11 patients. The duration of remission without hemodialysis was 6–12 months. Treatment with plasmapheresis in cases with recurrent anuria was without benefit. We can conclude that plasmapheresis can delay end‐stage renal failure in cases with acute onset of crescentic glomerulonephritis.
Platelet Adhesion, Contact Phase Coagulation Activation, and C5a Generation of Polyethylene Glycol Acid‐Grafted High Flux Cellulosic Membrane with Varieties of Grafting Amounts
Authors: Fushimi Fumiyoshi , Nakayama Mariko , Nishimura Kumiaki , Hiyoshi Tatsuo
Published: March 2003

Grafting of polyethylene glycol chains onto cellulosic membrane can be expected to reduce the interaction between blood (plasma protein and cells) and the membrane surface. Alkylether carboxylic acid (PEG acid) grafted high flux cellulosic membranes for hemodialysis, in which the polyethylene glycol chain bears an alkyl group at one side and a carboxyl group at the other side, have been developed and evaluated. PEG acid‐grafted high flux cellulosic membranes with various grafting amounts have been compared with respect to platelet adhesion, the contact phase of blood coagulation, and complement activation in vitro. A new method of quantitating platelet adhesion on hollow‐fiber membrane surfaces has been developed, which is based on the determination of lactate dehydrogenase (LDH) activity after lysis of the adhered platelets. PEG acid‐grafted high flux cellulosic membranes showed reduced platelet adhesion and complement activation effects in grafting amounts of 200 ppm or higher without detecting adverse effects up to grafting amounts of 850 ppm. The platelet adhesion of a PEG acid‐grafted cellulosic membrane depends on both the flux and grafting amounts of the membrane. It is concluded that the grafting of PEG acid onto a cellulosic membrane improves its biocompatibility as evaluated in terms of platelet adhesion, complement activation, and thrombogenicity.
Dynamic In Vitro and In Vivo Performance of a Permanent Total Artificial Heart
Authors: Rosenberg Gerson , Snyder Alan J. , Weiss William J. , Kusagawa Hitoshi , Rawhouser Marjorie A. , Prophet G. Allen , Mehta Sanjay , Reibson John D. , Clear Thomas J.
Published: March 2003

In vivo characterization studies were performed to compare the dynamic in vivo performance of the Penn State/3M Health Care electric total artificial heart to existing in vitro data. Fully implanted systems were utilized including the artificial heart, controller, backup batteries, compliance chamber, and transcutaneous energy transmission. Catheters were implanted to measure central venous pressure (CVP), left atrial pressure (LAP), right atrial pressure (RAP), pulmonary artery pressure (PAP), and aortic pressure (AoP). Cardiac output (CO) was determined from the implanted controller, and systemic vascular resistance (SVR) was calculated. Steady state data were collected for each animal along with data regarding the transient responses to changes in preload and afterload. Preload was manipulated through volume changes. Afterload changes were accomplished through vasoactive agents. Increased preload caused little change in cardiac output because the pump output was nearly maximum at baseline. LAP, AoP, and SVR increased with increasing RAP. Decreased preload caused a reduction in CO, LAP, and SVR. Afterload increase resulted in a slight decrease in flow and an increase in system power and SVR. Afterload reduction was accompanied by a decrease in preload and a concomitant reduction in flow. Overall, the system response was similar to the response observed in vitro.
Principles and Practice of Hemofiltration and Hemodiafiltration
Authors: Ledebo Ingrid
Published: March 2003

There is growing interest in the convective dialysis therapies, hemofiltration (HF) and hemodiafiltration (HDF). Both require dialysis membranes which are highly permeable to solutes as well as fluid, and in both cases large volumes of ultrafiltration are the condition for convective transport. In HDF the convection is combined with diffusion, and as a consequence, maximum clearance over the entire molecular weight spectrum is achieved. Optimal forms of HDF provide urea clearance 10–15% higher than the corresponding diffusive mode. The larger the solute, the greater is the impact of convection, and β2‐microglobulin
(β2m) levels may be up to 70% reduced. Traditional postdilution HF provides high clearance of medium sized and large molecules. Satisfactory clearance of small solutes requires blood flows in excess of 500 ml/min. With access to practically unlimited volumes of substitution solution through on‐line ultrafiltration, predilution HF can now be used. This increases the clearance of small solutes to an acceptable range. For HDF as well as HF, large patient populations consistently treated for longer periods of time are needed to make valid outcome comparisons with other therapies.
Hemodialysis‐Induced Hypophosphatemia in a Normophosphatemic Patient Dialyzed for Ethylene Glycol Poisoning: Treatment with Phosphorus‐Enriched Hemodialysis
Authors: Chow  , Lin  , Mitra  , Singh  , Lee  , Leehey  , Ing
Published: March 2003

It is the goal of this section to publish material that provides information regarding specific issues, aspects of artificial organ application, approach, philosophy, suggestions, and/or thoughts for the future.

Hypophosphatemia developed in a normophosphatemic patient after 9 h of hemodialysis therapy (using a phosphate‐free dialysate) administered for the treatment of ethylene glycol poisoning. The hypophosphatemia was promptly improved with additional hemodialysis treatment using a phosphorus‐enriched dialysate.
Effect of Ultrafiltration During Cardiopulmonary Bypass for Pediatric Cardiac Surgery
Authors: Watanabe Takashi , Sakai Yoshimasa , Mayumi Toshihiko , Shimomura Tsuyoshi , Song Min‐Ho , Tajima Kazuyoshi , Suenaga Yoshito , Kawaradani Yoshitaka , Saito Yasutaka , Yamada Teiji
Published: March 2003

The effect of ultrafiltration during cardiopulmonary bypass (CPB) was evaluated for correcting ventricular septal defects with associated pulmonary hypertension in patients less than 18 months old. Interleukin (IL)‐6 and IL‐8 concentrations in the blood, ultrafiltrate, and urine were measured. The blood IL‐6 concentration increased to 128.4 ± 20.2 pg/ml by the end of surgery, which is lower than the concentration seen in adult patients (273.1 ± 48.2 pg/ml, p < 0.02). The blood IL‐8 concentration was not significantly different than that of adults. The total amounts of excreted IL‐6 in the ultrafiltrate and urine during CPB were 11.5 ± 0.32 pg/kg and 0.32 ± 0.07 pg/kg, respectively (p < 0.05). The total amounts of excreted IL‐8 in the ultrafiltrate and urine were 4.64 ± 0.69 pg/kg and 1.92 ± 0.56 pg/kg, respectively (p < 0.05). No differences were seen in these values for excretion between children and adults. We conclude that ultrafiltration during CPB in pediatric patients is more effective in removing proinflammatory cytokines than in adults and more effective than renal filtration alone.