bluuebunny/crossref_metadata_2025 huggingface dataset:
The genome organization and diversification of maize and its allied species revisited: evidences from classical and FISH-GISH cytogenetic analysis
Authors: Poggio L. , Gonzalez G. , Confalonieri V. , Comas C. , Naranjo C.A.
Published: March 2005

The present review summarizes our classical and molecular cytogenetic investigations in the genus Zea. The results obtained from the meiotic behavior analysis of Zea species and hybrids, confirm the amphiploid nature of all species in the genus, with a basic number of x = 5 chromosomes. All species with 2n = 20 are diploidized allotetraploids, whereas Z. perennis (2n = 40) is an allooctoploid with four genomes somewhat divergent from one another. These analyses also revealed the existence of postzygotic reproductive isolation among Zea species. Our studies using genomic in situ hybridization (GISH) provide evidence about the evolutionary relationships among maize and its allied species, and reveal remarkable genomic divergences. Particularly, knob sequences were not completely shared between taxa previously considered to be closely related. Our data strongly suggest that the teosinte Z. mays parviglumis is not the only progenitor of cultivated maize. Introgression of Tripsacum into cultivated maize cannot be discarded.
Biogeographic distribution of polyploidy and B chromosomes in the apomictic Boechera holboellii complex
Authors: Sharbel T.F. , Mitchell-Olds T. , Dobeš C. , Kantama L. , de Jong H.
Published: March 2005

The Boechera holboellii complex comprises B. holboellii and B. drummondii, both of which can reproduce through sex or apomixis. Sexuality is associated with diploid individuals, whereas apomictic individuals are diploid or triploid and may additionally have B chromosomes. Using flow cytometry and karyotype analysis, we have shown that B chromosomes (a) occur in both diploid and triploid apomictic B. holboellii, (b) may occur in triploid B. drummondii, and (c) are dispensable for the plant. Both diploid and triploid karyotypes are found in multiple chloroplast haplotypes of both species, suggesting that triploid forms have originated multiple times during the evolution of this complex. B chromosome carriers are found in geographically and genetically distinct populations, but it is unknown whether the extra chromosomes are shared by common descent (single origin) or have originated via introgressive hybridization and repeated transitions from diploidy to triploidy. Diploid plants containing the Bs reproduce apomictically, suggesting that the supernumerary elements are associated with apomixis. Finally, our analyses of pollen size and viability suggest that irregular chromosome segregation in some triploid lineages may lead to the generation of diploid individuals which carry the B chromosomes.
Robertsonian translocations in wheat arise by centric misdivision of univalents at anaphase I and rejoining of broken centromeres during interkinesis of meiosis II
Authors: Friebe B. , Zhang P. , Linc G. , Gill B.S.
Published: March 2005

The mechanism of origin of Robertsonian translocations was investigated in plants monosomic for chromosome 1A of wheat and 1Ht of Elymus trachycaulus by GISH. Chromosomes 1A and 1Ht stayed univalent in all metaphase I cells analyzed, suggesting that Robertsonian translocations do not originate from meiotic recombination in centromeric regions with shared DNA sequence homology. At ana-/telophase I, the 1Ht and 1A univalents underwent either chromosome or chromatid segregation and misdivided in 6–7% of the pollen mother cells. None of the ana-/telophases I analyzed had Robertsonian translocations, which were only observed in 2% of the “half tetrads” at ana-/telophase II. The frequency of Robertsonian translocations observed at ana-/telophase II corresponds well with the number of Robertsonian translocations (1–4%) detected in progenies derived from plants monosomic for group-1 chromosomes of wheat (1A, 1B, and 1D) and 1Ht of E. trachycaulus. Our data suggest that Robertsonian translocations arise from centric misdivision of univalents at ana-/telophase I, followed by segregation of the derived telocentric chromosomes to the same nucleus, and fusion of the broken ends during the ensuing interkinesis.
Molecular cytogenetics and tandem repeat sequence evolution in the allopolyploid Nicotiana rustica compared with diploid progenitors N. paniculata and N. undulata
Authors: Lim K.Y. , Matyasek R. , Kovarik A. , Fulnecek J. , Leitch A.R.
Published: March 2005

Nicotiana rustica (2n = 4x = 48) is a natural allotetraploid composed of P and U genomes which are closely related to genomes of diploid species N. paniculata and N. undulata. Genomic in situ hybridization (GISH) also confirms that the diploid parents, or close relatives, are the ancestors of N. rustica. In order to study genetic interactions between ancestral genomes in the allotetraploid, we isolated three families of repetitive sequences, two from N. paniculata (NPAMBE and NPAMBO) and one from N. undulata (NUNSSP). Southern blot hybridization revealed that the sequences are digested with a range of restriction enzymes into regular ladder patterns indicating a tandem arrangement of high copy repeats possessing monomeric units of about 180 bp. The three-tandem sequences belong to a larger Nicotiana tandem repeat family called here the HRS-60 family. Members of this family are found in all Nicotiana species studied. Fluorescence in situ hybridization (FISH) analysis localized the satellite repeats to subtelomeric regions of most chromosomes of N. paniculata and N. undulata. The pattern of sequence distribution on the P- and U-genomes of N. rustica was similar to the putative parents N. paniculata and N. undulata respectively. However, NPAMBO repeats appear to be reduced and rearranged in N. rustica that may suggest evolution within the P genome. GISH and FISH with the tandem repeat probes failed to reveal intergenomic translocations as might be predicted from the nucleocytoplasmic interaction hypothesis.
Wheat cytogenetics in the genomics era and its relevance to breeding
Authors: Gupta P.K. , Kulwal P.L. , Rustgi S.
Published: March 2005

Hexaploid wheat is a species that has been subjected to most extensive cytogenetic studies. This has contributed to understanding the mechanism of the evolution of polyploids involving diploidization through genetic restriction of chromosome pairing to only homologous chromosomes. The availability of a variety of aneuploids and the ph mutants (Ph1 and Ph2) in bread wheat also allowed chromosome manipulations leading to the development of alien addition/substitution lines and the introgression of alien chromosome segments into the wheat genome. More recently in the genomics era, molecular tools have been used extensively not only for the construction of molecular maps, but also for identification/isolation of genes/QTLs (including epistatic QTLs, eQTLs and PQLs) for several agronomic traits. It has also been possible to identify gene-rich regions and recombination hot spots in the wheat genome, which are now being subjected to sequencing at the genome level, through development of BAC libraries. In the EST database also, among all plants wheat ESTs are the highest in number, and are only next to those for human, mouse, Ciona intestinalis (a chordate), rat and zebrafish genomes. These ESTs and sequences of several genomic regions have been subjected to a variety of applications including development of perfect markers and establishment of microcollinearity. The technique of in situ hybridization (including FISH, GISH and McFISH) and the development of deletion stocks also facilitated the preparation of physical maps. Molecular markers are also used for marker-assisted selection in wheat breeding programs in several countries. Construction of a wheat DNA chip, which will also become available soon, may further facilitate wheat genomics research. These enormous resources, knowledge base and the fast development of additional molecular tools and high throughput approaches for genotyping will prove extremely useful in future wheat research and will lead to development of improved wheat cultivars.
Recent progress in barley improvement using wild species of Hordeum
Authors: Pickering R. , Johnston P.A.
Published: March 2005

In this review we describe recent progress in barley (Hordeum vulgare) improvement through hybridisation with its wild relatives. We have focused on one species in the secondary genepool of cultivated barley, namely H. bulbosum. This wild species has desirable traits, such as disease resistance, that are worthwhile transferring to its cultivated relative. Progress has been achieved through developing partially fertile interspecific hybrids that have been selfed or backcrossed to barley. We present the results of cytogenetic and molecular analyses that have enabled us to characterise and produce agronomically useful recombinant lines obtained from the hybrids.
Limitations of in situ hybridization with total genomic DNA in routine screening for alien introgressions in wheat
Authors: Lukaszewski A.J. , Lapinski B. , Rybka K.
Published: March 2005

In situ hybridization with total genomic DNA (GISH) has become a powerful tool in characterization of alien introgressions in wheat. With recent simplification it can now be used in large scale screening for new chromosome constructs. Its level of resolution in routine applications was tested on sets of recombined wheat-rye chromosomes with genetically determined positions of the translocation breakpoints. The resolution level of GISH visualized by an enzymatic color reaction was much lower than that of GISH with fluorescent probes but both techniques failed to reveal the presence of some distally located breakpoints. The limits of resolution for the two methods were at least 9.8 and 3.5 cM of the relative genetic lengths of chromosome arms, respectively, in configurations with proximal rye and terminal wheat segments when rye DNA was used as a probe. When wheat DNA was used as a probe, a terminal wheat segment estimated to be ca. 1.6 cM in length could not be visualized. An example of induced recombination between a chromosome of Agropyron elongatum and wheat illustrates that these resolution limits of GISH may hamper isolation of critical translocation breakpoints in a chromosome engineering effort.
Efficacy of Fluoride Toothpaste in Preventing Demineralization of Smooth Dentin Surfaces and Narrow Grooves in situ under Frequent Exposures to Sucrose or Bananas
Authors: Zaura E. , van Loveren C. , ten Cate J.M.
Published: March 2005

The use of models simulating fissures allows studying demineralization at sites that are most prone to caries in vivo. In practice, most in situ models use flat surfaces. Our objectives were: (1) to compare the demineralizing potential of sucrose solution with that of bananas and (2) to study the effect of fluoride toothpaste on demineralization in situ in an easily accessible site and a plaque stagnation site. Four volunteers wore bovine dentin specimens with narrow grooves and a smooth surface for two 1-week in situ periods, with eight 1-min sugar exposures daily: either by a rinse with 10% sucrose, or by consumption of a piece of banana. Twice daily, the appliance was dipped in toothpaste slurry of a control (fluoride-free) toothpaste at one side and a fluoride toothpaste at the contralateral side. Demineralization was assessed by transversal microradiography. We found no difference in dentin demineralization after frequent exposure to either sucrose solution or bananas. Fluoride toothpaste effectively protected dentin only at the smooth surface. In the grooves, fluoride affected the demineralization pattern; it drove lesions towards the bottom of the groove. We conclude that assessing only smooth surfaces in intraoral tests might lead to underestimated food cariogenicity and to overestimated efficacy of fluoride-containing toothpaste.
Postmyocardial Infarction Mortality in Relation to Depression: A Systematic Critical Review
Authors: Sørensenf Claus , Friis-Hasché Erik , Haghfelt Torben , Bech Per
Published: March 2005

The aim of this review was to survey the literature on depression in patients with myocardial infarction to assess the methodological quality and to test whether depression leads to an increased postmyocardial infarction mortality. Medline, Psycinfo, and www.UMI.com were searched, and researchers were contacted in the autumn of 2003. Thirty-one articles were reviewed. Only seven articles scored above a predefined level of 75% for acceptable quality. The articles lack description of non-responders, recall period for depressive symptoms, validation of applied instrument on target population, and sample size large enough to show differences between groups. The prevalence rates of depression ranged from 1.6 to 50%. In eight articles, a diagnostic test was applied, in the rest of the studies, questionnaires were used. The prevalence of depression was highest in those using patient-completed questionnaires. A significant positive association was shown between depression and postmyocardial infarction mortality in 15 studies, a non-significant association in 14, and in two articles, this was not reported. In articles with data collection starting after 1994, a non-significant relation tended to be reported. The studies were generally not of acceptable quality. They lacked sufficient power to show differences in stated end points between groups. Application of non-validated instruments caused large differences in prevalence rates of depression. Future studies should include a minimum of 1,000 patients, use a validated instrument, re-examine the patients, and describe participants and non-participants in detail.
Use of the Diagnostic Criteria for Psychosomatic Research in Oncology
Authors: Grassi Luigi , Sabato Silvana , Rossi Elena , Biancosino Bruno , Marmai Luciana
Published: March 2005

Background: Psycho-oncology literature has shown that 30–50% of cancer patients meet the criteria for a psychiatric diagnosis, according to the usual nosographic classification (e.g. DSM). The Diagnostic Criteria for Psychosomatic Research (DCPR) have been shown to be useful in identifying psychological constellations in patients with medical illness. The aims of the study were to compare the DSM-IV and the DCPR in their application to cancer patients. Method: One hundred and forty-six patients with cancer underwent semistructured interviews to assess psychiatric morbidity and psychosocial syndromes according to the DSM-IV and the DCPR, respectively. The Brief Symptom Inventory (BSI) was also used to assess psychological stress symptoms. Results: Sixty-five subjects (44.5%) met the criteria for a DSM-IV diagnosis (DSM cases), while 104 patients (71.2%) presented symptoms meeting the criteria for at least one DCPR syndrome. Three DCPR dimensions were more frequent than others, specifically Health Anxiety (37.7%), Demoralization (28.8%) and Alexithymia (26%). Among the subjects with no formal DSM-IV diagnosis (n = 81), 58% had at least one DCPR syndrome. DSM-IV cases had higher scores on several BSI subscales in comparison with patients with only one DCPR syndrome, while no difference was found in patients with more than one DCPR diagnosis. Conclusions: The DCPR system was found to be useful in oncology in investigating psychological conditions which are not identified by the DSM-IV alone. Assessment of more specific constructs, other than intensity of general stress symptoms, may give more specific information and help in tailoring psychological intervention for patients with cancer.
Persistent Cognitive Dysfunctions in Bipolar I Disorder and Schizophrenic Patients: A 3-Year Follow-Up Study
Authors: Balanzá-Martínez Vicente , Tabarés-Seisdedos Rafael , Selva-Vera Gabriel , Martínez-Arán Anabel , Torrent Carla , Salazar-Fraile José , Leal-Cercós Carmen , Vieta Eduard , Gómez-Beneyto Manuel
Published: March 2005

Background: Neurocognitive impairment has consistently been considered a central and stable feature in schizophrenia. As this possibility has been far less studied in bipolar disorder, we aimed to prospectively investigate the stability and specificity of cognitive performance in bipolar disorder compared to schizophrenia. Methods: Fifteen DSM-IV bipolar type I patients and 15 schizophrenic patients were assessed twice with a comprehensive neuropsychological battery and the Positive and Negative Syndrome Scale over a 3-year follow-up. The cognitive performance of the groups was compared at baseline and 3 years later as a mean with that of 26 healthy volunteers. Endpoint and baseline assessments were also compared for each patient group in order to evaluate the stability of cognitive impairment. Results: At both time points, bipolar and schizophrenic patients showed significant deficits on most of the cognitive tasks compared to healthy subjects. Overall, the cross-sectional cognitive profile was similar for both patient groups. Moreover, after controlling for age and length of illness, the two groups’ cognitive function did not differ over time in any test. With the exception of the Stroop color-word interference task, performance at baseline for each test but neither length of illness nor diagnostic category predicted the endpoint performance. Conclusion: This preliminary study suggests that cognitive impairment is also mainly stable over time in bipolar I disorder and thus not specific to schizophrenia.
Assessing the Community Prevalence of Bipolar Spectrum Symptoms by the Mood Disorder Questionnaire
Authors: Mangelli Lara , Benazzi Franco , Fava Giovanni A.
Published: March 2005

Background: The goal of this study was to assess the frequency and spectrum of symptoms related to bipolar disorders in a community sample by means of a self-rating questionnaire. Method: The Mood Disorder Questionnaire, a self-rating scale which evaluates DSM-IV manic/hypomanic symptoms, was administered to a community sample of 1,034 individuals recruited through advertisements. Symptom interrelationships were studied by factor analysis. Results: 275 individuals (26.6%) reported moderate or severe impairment due to the symptoms. Manic/hypomanic symptoms were present in a high proportion of individuals. Factor analysis found a two-factor structure of bipolar spectrum symptoms (an elevated mood overactivity factor, and an irritable behavior factor). Conclusion: The findings of this study highlight the need of complementing clinical investigations on the bipolar spectrum with community studies. Subclinical manic-hypomanic symptoms may be present also in allegedly unipolar patients and may have implications on the course of illness.
Increased Maintenance of Obsessive-Compulsive Disorder Remission after Integrated Serotonergic Treatment and Cognitive Psychotherapy Compared with Medication Alone
Authors: Biondi Massimo , Picardi Angelo
Published: March 2005

Background: Both medication and psychotherapy are effective in obsessive-compulsive disorder (OCD). However, they both have disadvantages. We aimed at studying the long-term effectiveness of integrated treatment compared with medication alone. Methods: A private practice sample of 20 consecutive patients with OCD (DSM-III-R) who achieved remission or marked improvement [Yale-Brown Obsessive-Compulsive Scale (YBOCS) score ≤10 and Global Assessment of Functioning (GAF) scale score ≧70] after drug treatment (clomipramine or selective serotonin reuptake inhibitors for 12–24 months) with or without concurrent cognitive psychotherapy were followed up. In the integrated treatment group, psychotherapy was started on the second or third visit and was timed to end after medication. Efforts were applied to integrate treatments within a biopsychosocial theoretical framework. As randomisation was not feasible in the study setting, treatment allocation was based on patients’ preference. Patients were assessed before treatment, after treatment and at each follow-up contact with the YBOCS, the Hamilton Depression Rating Scale, and the GAF scale. Kaplan-Meier survival analysis was performed on the time to OCD relapse. Results: Of the factors studied (gender, age, duration of disorder, severity of OCD symptoms at baseline), only treatment was associated with outcome. Of 10 patients treated with medication alone, 8 relapsed. Of 10 patients who received integrated treatment, only 1 relapsed. The estimated mean survival time was significantly higher (p < 0.001) in the integrated treatment group (132 months, 95% CI 107–157) than in the medication group (25 months, 95% CI 12–38). Conclusions: Although our results need confirmation by further, more robust studies, the long-term superiority of integrated treatment over medication alone was large. Patients with OCD might have viable options other than long-term drug treatment.
Strategic Targets of Essential Host-Pathogen Interactions
Authors: Blasi Francesco , Tarsia Paolo , Aliberti Stefano
Published: March 2005

This review summarizes the present concepts regarding the biological processes that mediate intrinsic and innate host defense against microbial invasion of the lung. Innate immunity is the first line of defense of the higher organisms towards invading pathogens. It accomplishes a wide variety of activities including recognition and effector functions. The innate responses use phagocytic cells (macrophages, monocytes, and neutrophils), cells that release inflammatory mediators (basophils, mast cells, and eosinophils), and natural killer cells. The molecular component of innate responses includes complement, acute-phase proteins, and cytokines. Recognition of pathogen-associated molecular patterns is mediated by the pathogen receptors of the innate immune system, among these molecules toll-like receptors have emerged as fundamental components in the innate immune responses to infection, and a link between innate and adaptive immunity. Additional protection comes from polypeptide mediators of the innate host defense, such as the defensins and other antibiotic peptides. In view of the considerable burden in terms of mortality and morbidity that severe infections still pose worldwide, a better understanding of the biological basis of host-pathogen interactions opens stimulating future treatment perspectives.
Induced Sputum versus Bronchoalveolar Lavage Fluid in the Evaluation of Patients with Idiopathic Pulmonary Fibrosis
Authors: Antoniou Katerina M. , Alexandrakis Michaels , Tzanakis Nikolaos , Tsiligianni Ioanna , Tzortzaki Eleni G. , Siafakas Nikolaos M. , Bouros Demosthenes E.
Published: March 2005

Background: Induced sputum (IS) has been proposed as a useful noninvasive method for the assessment of airway diseases. Bronchoalveolar lavage fluid (BALF), an important tool for evaluating interstitial lung diseases, has limited utility due to its invasiveness and the difficulties of performing it in severely ill patients, while it is impractical for follow-up evaluation. Objectives: The aim of this study was to investigate the differences and the possible correlation of cell differential and lymphocyte subpopulations between BALF and IS samples in patients with idiopathic pulmonary fibrosis (IPF). Methods: We studied prospectively 20 patients (18 male, 2 female) of median age 67 years (range 40–75) with IPF and 10 normal subjects (5 female, 5 male) of median age 59 years (range 36–70). IS was performed with hypertonic saline solution using an ultrasonic nebulizer (Ultraneb 2000). BALF was performed by a conventional procedure using fiberoptic bronchoscopy within 3 days from IS. May-Grünewald-Giemsa-stained preps were differentially counted and T-lymphocyte subsets were analyzed by a flow-activated cell sorter. Results: The percentage of macrophages was significantly lower in IS than in BALF (p < 0.0001), while the neutrophils were lower in BALF (p < 0.0001). A significant correlation was found between BALF and IS eosinophil counts (r = 0.54, p = 0.01) and CD4+/CD8+ ratio (r = 0.74, p < 0.0001). Conclusion: Our data suggest that different information is obtained by IS and BALF and thus, the two methods are complementary in IPF.
Increased Levels of Interleukin-18 in Bronchoalveolar Lavage Fluid of Patients with Idiopathic Nonspecific Interstitial Pneumonia
Authors: Ishii Hiroshi , Mukae Hiroshi , Kadota Jun-ichi , Fujii Takeshi , Abe Koh , Ashitani Jun-ichi , Kohno Shigeru
Published: March 2005

Background: Interleukin-18 (IL-18) is a proinflammatory cytokine that can induce interferon-γ (IFN-γ), and it plays an important role in T-helper 1 responses. Among idiopathic interstitial pneumonia (IIP), nonspecific interstitial pneumonia (NSIP) has an increased number of lymphocytes in bronchoalveolar lavage (BAL) fluid compared with usual interstitial pneumonia (UIP). However, the difference in their pathogenesis is unclear. Objective: The present study aims to investigate the roles of IL-18 in patients with idiopathic UIP and idiopathic NSIP. Methods: We measured the serum and BAL fluid (BALF) levels of IL-18 and IFN-γ in 22 patients with IIP (12 with UIP, 10 with NSIP) and 9 healthy volunteers. Results: Lymphocyte proportions in BALF were significantly higher in NSIP than in UIP and healthy subjects. No significant differences were observed in the serum IL-18 levels of all subjects, while the BALF levels of IL-18 in patients with NSIP were significantly higher than in patients with UIP (p < 0.005) and in healthy subjects (p < 0.005). Among all subjects, the levels of IL-18 in BALF correlated significantly with those in serum and the lymphocyte proportions in BALF. The serum IFN-γ levels of all subjects were below sensitivity, but there was significant reverse correlation between the levels of IFN-γ and the lymphocyte proportions in BALF. Conclusion: The lymphocytosis in BALF of patients with idiopathic NSIP and a part of idiopathic UIP might be associated with the high levels of IL-18.
Determinants of the Length of Mechanical Ventilation in Patients with COPD in the Intensive Care Unit
Authors: Gursel Gul
Published: March 2005

Background: About 10% of the patients with chronic obstructive pulmonary disease (COPD) are at high risk for prolonged mechanical ventilation (MV >21 days), and mortality ranges from 55 to 78% in these patients. Objective: To determine the potential risk factors for MV over periods of 1, 2 and 3 weeks in patients with COPD. Patients and Method: The characteristics of patients during the stable period of their disease, on admission to the intensive care unit (ICU) and during the ICU stay were recorded prospectively and analyzed retrospectively for this study. t test, XXX2 test and logistic regression analysis were used for statistical analysis. Results: 86 patients with COPD requiring MV were included in the study. 73, 33, and 13% of the patients required MV longer than 1, 2 and 3 weeks, respectively. There were no significant relationships between the duration of MV and bronchiectasis or the presence of community-acquired pneumonia on admission, baseline pulmonary function test results or blood gas parameters on admission. Development of ventilator-associated pneumonia (VAP; odds ratio, OR: 6; 95% confidence interval, CI: 2–23, p = 0.011) and sepsis (OR: 10; 95% CI: 2–54, p = 0.007) were independent predictors for MV >7 days. VAP was still a risk factor for MV >15 days with an OR of 14 (95% CI: 3–66, p = 0.001). On the other hand MV >21 days was primarily determined by increasing age (OR: 1.2; 95% CI: 1–1.3, p = 0.042), severity of the disease on admission measured by APACHE II score (OR: 1.4; 95% CI: 1–1.7, p = 0.002) and albumin levels (OR: 0.10, 95% CI: 0.01–0.54, p = 0.007). Conclusion: Advanced age, severity of disease on admission and development of VAP during ICU stay are the main determinants of MV duration in patients with COPD.
Role of cdk4, p16INK4, and Rb Expression in the Prognosis of Bronchioloalveolar Carcinomas
Authors: Ghazizadeh Mohammad , Jin Enjing , Shimizu Hajime , Fujiwara Masakazu , Arai Satoru , Ohaki Yoshiharu , Takemura Tamiko , Kawanami Oichi
Published: March 2005

Background: The p16INK4 protein has been identified as a potent inhibitor of cyclin-dependent kinase (cdk)4 by blocking cdk4-mediated phosphorylation of the tumor suppressor retinoblastoma (Rb) protein, thus allowing Rb-mediated growth suppression. Objectives: Loss of p16INK4 has been associated with a poor cancer prognosis, but its potential significance in bronchioloalveolar carcinomas (BACs) has not been explored. Methods: We examined immunohistochemical expression of p16INK4, cdk4, and Rb proteins in 38 BACs and correlated their expression levels with known clinicopathological features of the disease. Results: All BACs expressed cdk4, while 89 and 82% expressed p16INK4 and Rb proteins, respectively. None of the clinicopathological factors correlated with p16INK4, cdk4, or Rb expression separately. A low p16INK4/cdk4 ratio was significantly associated with a high disease stage (p = 0.04), and the ratio tended to be lower in mucinous than nonmucinous tumors. BACs with a low p16INK4/cdk4 ratio showed significantly higher Rb expression levels (p = 0.02). Univariable survival analyses showed a significantly lower 5-year survival probability in patients with a high stage (p = 0.002) or low p16INK4/cdk4 ratio (p = 0.01). Conclusions: The results suggest a role of the cdk4/p16INK4 pathway in the prognosis of BACs. Further studies are warranted to clarify whether a low p16INK4/cdk4 ratio may identify tumors that are destined to behave unfavorably.
Antioxidant Responsiveness in BALB/c Mice Exposed to Ozone
Authors: Jang An-Soo , Choi Inseon-S. , Yang Sung-Yeul , Kim Young-Gon , Lee June-Hyuk , Park Sung-Woo , Park Choon-Sik
Published: March 2005

Background: A single, acute exposure to ozone has been shown to modify the antioxidant defense mechanism in the respiratory tract. Objective: The aim of this study was to evaluate the effects of ozone exposure on antioxidant response in BALB/c mice. Methods: We measured enhanced pause of breathing (Penh) as a marker of airway obstruction using barometric whole-body plethysmography before and after ozone exposure [groups (n = 6): filtered air, 0.12 ppm, 0.5 ppm, 1 ppm, 2 ppm] for 3 h. Antioxidant levels were measured using high-performance liquid chromatography with electrochemical detection in bronchoalveolar lavage (BAL) fluid and lung tissue homogenates. Results: Malondialdehyde concentrations in lung tissue homogenates were significantly increased in the group exposed to 2-ppm ozone compared to the filtered air group. Uric acid and γ-tocopherol concentrations in BAL fluid were significantly increased in the ozone exposure group compared to the filtered air group (p < 0.01). Uric acid concentrations were increased in a concentration-dependent manner according to ozone concentration to which the animals were exposed. Increases in Penh after ozone exposure were significantly higher in an ozone concentration-dependent manner. The proportion of neutrophils in BAL fluid was significantly higher in the group exposed to 2 ppm than in the filtered air and the group exposed to 0.12 ppm (p < 0.01, respectively). The level of ascorbate correlated with the level of γ-tocopherol. Conclusion: These findings suggest that antioxidant responses may serve as a protective mechanism against a range of oxidants in BALB/c mice exposed to ozone.
Pulmonary Malakoplakia Coexistent with Tuberculosis of the Hilar Lymph Node Mimicking Malignancy
Authors: Pang Leou-Chuan
Published: March 2005

Pulmonary malakoplakia is a disease that is difficult to diagnose because its symptoms vary from those mimicking bronchogenic carcinoma to pneumonitis-like tuberculous infections. Malakoplakia is an unusual inflammatory condition characterized by the accumulation of macrophages with diagnostic Michaelis-Gutmann bodies. In this study, an immunocompromised patient with a tumor mass in the upper lobe of the right lung coexisting with hilar node enlargement is presented. A thoracoscopic biopsy revealed pulmonary malakoplakia with tuberculosis of the hilar lymph node. Microbiologic cultures were positive for acid-fast positive bacilli from the hilar node specimen, and negative for any other microorganisms such as Rhodococcus equi, but positive for Escherichia coli from the lung specimen. The significance of these findings and the coincidental association between malakoplakia and tuberculosis are discussed.
Screening for Single Gene Genetic Disease
Authors: Musci Thomas J.
Published: March 2005

The screening and directed testing for genetic disease caused by single gene mutations is an expanding part of the overall scheme of prenatal care. In addition to reproductive choice, carrier screening and fetal diagnostic testing afford the important opportunity for preparation of the family and the delivery site for the birth of a fetus with a known genetic disorder. Increasingly the primary care provider in pregnancy bears the burden of engaging patients in discussions regarding available genetic tests appropriate to their family or personal history, their ethnic group, and with every patient for a limited but growing number of diseases. Ethnic-based risk identification and testing has expanded recently with, for example, the addition of familial dysautonomia for patients of Askhenazi ancestry. Widespread, or nearly universal, screening has emerged for cystic fibrosis and new initiatives are gaining momentum for prenatal maternal carrier screening for fragile X syndrome. The fruits of the human genome project will undoubtedly lead to the identification of more genes that underlie human disease. This will expand the menu of possible prenatal testing options and will raise the level of complexity in both counseling, testing logisitics and health care resource allocation.
Fistulizing Crohn’s Disease
Authors: Felley Christian , Mottet Christian , Juillerat Pascal , Froehlich Florian , Burnand Bernard , Vader John-Paul , Michetti Pierre , Gonvers Jean-Jacques
Published: March 2005

Fistulas are common in Crohn’s disease. A population-based study has shown a cumulative risk of 33% after 10 years and 50% after 20 years. Perianal fistulas were the most common (54%). Medical therapy is the main option for perianal fistula once abscesses, if present, have been drained, and should include antibiotics (both ciprofloxacin and metronidazole) and immunomodulators. Infliximab should be reserved for refractory patients. Surgery is often necessary for internal fistulas.
Obstructive Fibrostenotic Crohn’s Disease
Authors: Froehlich Florian , Juillerat Pascal , Mottet Christian , Felley Christian , Vader John-Paul , Burnand Bernard , Gonvers Jean-Jacques , Michetti Pierre
Published: March 2005

Crohn’s disease is often complicated by gastrointestinal strictures. Postoperative recurrence at the anastomotic site is common and repeated surgical interventions may be necessary. Medical treatment may relieve active inflammation (see chapter on active luminal disease) but fibrous strictures will not respond to this. Mechanical treatment methods consist of endoscopic balloon dilation, stricturoplasty or surgical resection. Fibrostenotic Crohn’s disease does not respond to medical therapy and requires endoscopic or surgical treatment.
When to Measure Lipid Profile after Stroke?
Authors: Yan Bernard , Parsons Mark , McKay Sharyn , Campbell Donald , Infeld Bernard , Czajko Raymond , Davis Stephen M.
Published: March 2005

Background:Although acute decreases in total cholesterol (TC) are well documented in myocardial infarction, previous stroke studies have produced conflicting results. The timing of lipid estimation in ischemic stroke is becoming important with recent trial results indicating the benefits of statins. We therefore aimed to determine the optimal time for lipid measurements after stroke. We hypothesized that TC would acutely decrease after stroke and return to baseline by 12 weeks. Methods and Results: We performed a prospective, observational study of 50 patients (age 68.5 ± 11.2 years) who presented with acute ischemic stroke. Of these, 22 (44%) were HMG-CoA reductase (statin) naïve, 15 (30%) had already been on statins and 13 (26%) were commenced on statins. Of the 50 patients, 38 (76%) completed 12 weeks of follow-up, 5 died, and 7 were lost to follow-up. Fasting lipid profile (TC, low-density lipoprotein, high-density lipoprotein, triglyceride) was measured <48 h, 4 weeks and 12 weeks following ictus. In patients who were statin naïve, there was a significant increase in TC at the week 12 evaluation. Conclusions: Cholesterol levels in acute stroke are an unreliable measure of lipid status. Initiation of statins should ideally be based on measurements taken 12 weeks after stroke.
Severe Umbilical Cord Acidemia and Neurological Outcome in Preterm and Full-Term Neonates
Authors: Lavrijsen Selma W. , Uiterwaal Cuno S.P.M. , Stigter Robert H. , de Vries Linda S. , Visser Gerard H.A. , Groenendaal Floris
Published: March 2005

Background: Severe intrauterine hypoxia-ischemia and acidemia may lead to a disturbed neurodevelopment. Objectives: To study the effects of acidemia at birth on neurodevelopment in preterm and full-term neonates. Subjects and Methods: Short- and long-term outcome were studied retrospectively in 44 inborn preterms and 95 full-terms with severe acidemia at birth defined as a pH of the umbilical artery <7.00. Outcome was compared with 67 preterm and 90 full-term non-acidemic neonates (pH > 7.15). Intraventricular hemorrhage (preterms) or seizures (both preterms and full-terms) were considered an adverse short-term outcome. Neonatal death, cerebral palsy or neurodevelopmental delay were considered an adverse long-term outcome. Results: Severe intraventricular hemorrhage (IVH) occurred in 5 of the 44 (11%) acidemic preterms and in none of the 67 (0%) non-acidemic preterms (p < 0.01). Seizures were observed in 9 of the 44 (20%) and 11 of the 95 (12%) acidemic preterms and full-terms, respectively, and in none of the 67 (0%) and 1 of the 90 (1%) non-acidemic preterms and full-terms, respectively (p < 0.001 for preterms, p < 0.01 for full-terms). Nine preterms (6 acidemic, 3 non-acidemic) and 2 full-terms (both acidemic) died in the neonatal period. Adverse long-term outcome occurred in 32% of the acidemic preterms, in 21% of the non-acidemic preterms, in 7% of the acidemic full-terms and in 7% of the non-acidemic full-terms. Conclusions: Acidemia at birth increased the occurrence of severe IVH in preterm neonates and seizures in both preterm and full-term neonates. However, no significant effect of acidemia on long-term outcome could be demonstrated.
Influence of Different Haemodialysis Modalities on AGE Peptide Levels: Intradialytic versus Long-Term Results
Authors: van Tellingen Anne , Schalkwijk Casper G. , Teerlink Tom , Barto Rob , Grooteman Muriel P.C. , van der Ploeg Tjeerd , ter Wee Piet M. , Nubé Menso J.
Published: March 2005

Background: Peptide-linked degradation products of advanced glycation end products (AGE peptides) accumulate in chronic haemodialysis (HD) patients and may contribute to a number of HD-related long-term complications, such as accelerated atherosclerosis. Methods: The influence of a single HD session versus long-term HD on serum AGE peptides was determined. The patients were randomized to HD with a low-flux polysulfone (PS; F 6HPS), a high-flux PS (F 60S), a superflux PS (F 500S), or a superflux cellulose triacetate (CTA; Tricea 150G) dialyzer. Results: During a single HD session, both AGE peptides and reference peptides decreased significantly (AGE peptides: Tricea 150G –37.0 ± 2.9%; F 6HPS –35.5 ± 2.4%; F 60S –39.5 ± 4.7%, and F 500S –43.3 ± 2.1%, p = 0.005; reference peptides: Tricea 150G –73.2 ± 8.8%; F 6HPS –73.2 ± 7.9%; F 60S –72.5 ± 8.2%, and F 500S –74.1 ± 7.3%, p = 0.005). After 12 weeks of HD with the superflux CTA, the AGE peptide levels decreased significantly (week 1: 2.7 ± 1.1 arbitrary units, week 12: 2.5 ± 1.2 arbitrary units, decrease 7.4%; p = 0.01), whereas the AGE peptide levels remained unchanged after HD with each of the other three modalities. The reference peptide levels did not change after 12 weeks of HD. Conclusion: Although AGE peptides can be effectively removed during a single HD session, superflux CTA seems to be the only modality capable of reducing AGE peptides in the long term.
A Comparison Study of Nonanoic Acid and Sodium Lauryl Sulfate in Skin Irritation
Authors: Lee Cheol Heon , Kim Hyun Wook , Han Hee Jin , Park Chun Wook
Published: March 2005

The cutaneous response to irritants can be influenced by various factors including the characteristic of irritants, the mode of exposure, environmental and host-related factors. It has been suggested that irritants can be divided into two types: corrosive and noncorrosive. Sodium lauryl sulfate (SLS) has been considered as a typical corrosive irritant and nonanoic acid (NAA) an example of a noncorrosive irritant. We applied SLS and NAA solutions on the volar forearm skin for 24 h and measured transepidermal water loss (TEWL) and erythema indices to evaluate some differences in the profile of irritant reaction and skin functions between corrosive and noncorrosive irritation. In our study of TEWL measurements, SLS solutions caused higher TEWL values than NAA solutions, and the slope of the SLS curve was steeper than that of the NAA curve in relation to the concentrations of SLS and NAA. There was a tendency for the TEWL values to plateau at higher NAA concentrations. In the study of the time course of TEWL and erythema indices, TEWL values returned to baseline after 3 weeks in areas patch-tested with 50% NAA, but they did not recover baseline values until 3 weeks in the corresponding areas tested with 5% SLS. However, both SLS and NAA solutions showed a very similar pattern of erythema indices. Our data suggest that skin injuries induced by SLS might need a more prolonged recovery time for TEWL than NAA injuries. SLS, the corrosive irritant, showed a different pattern of cutaneous functional change compared with NAA, the noncorrosive irritant. NAA could also be considered as one of the model irritants in a study of irritant contact dermatitis using a noncorrosive irritant.
Treatment of Non-Atypic Endometrial Hyperplasia Using Thermal Balloon Endometrial Ablation Therapy
Authors: Järvelä Ilkka Y. , Santala Markku
Published: March 2005

Background/Aim: Traditionally endometrial hyperplasias have been treated with progestins. Unfortunately, quite often hyperplasias are resistant to treatment, or they recur after therapy. The aim of the study was to compare traditional progestin administration with thermal balloon endometrial ablation in the treatment of non-atypic endometrial hyperplasia. Methods: Women with endometrial hyperplasia (n = 34) were randomized in a 1:1 allocation ratio. Endometrial biopsy samples were taken 6 and 12 months after the treatment; if any signs of hyperplasia were detected, hysterectomy was performed. In addition, the hospital records were checked in September 2003 to observe for any later hysterectomy. Main outcome measures wererecovery from hyperplasia and avoidance of hysterectomy. Results: In patients treated with thermal ablation, the hyperplasias persisted at 6 or 12 months in 4 out of 17 patients, whereas the rate was 6 out of 17 patients in the progestin therapy group. According to patient records, 1 further patient treated with thermal ablation and 3 further patients treated with progestin were hysterectomized after the last visit. A total of 14 of the 34 patients (41%) have been hysterectomized so far. Conclusions: These preliminary results suggest that thermal balloon endometrial ablation therapy seems to be as effective as traditional progestin administration in the treatment of non-atypic endometrial hyperplasia. The hysterectomy rate during the follow-up period was, however, considerably high, and, therefore, hysterectomy might be considered even a first-choice treatment for endometrial hyperplasias.
Basal Prolactin Values Correlate with Response to Reboxetine Treatment in Major Depression, but Not with Response to Citalopram
Authors: Moeller Olaf , Hetzel Guenter , Michael Nikolaus , Rothermundt Matthias , Arolt Volker , Erfurth Andreas
Published: March 2005

Little is known about variables that might predict outcome in major depression. Recently, basal prolactin values (BPV) have been suggested to predict response to treatment with tricyclic antidepressive drugs. In order to examine whether BPV predict response to selective mono-aminergic therapy, 24 in-patients with major depression were treated in a single-masked, randomised study using the most selective noradrenergic or serotonergic reuptake inhibitors available for antidepressant treatment, i.e. reboxetine and citalopram. A significant correlation between BPV and treatment response to reboxetine was found, but not between BPV and response to citalopram. As BPV are influenced by noradrenergic activity, it can be hypothesized that depressed patients with comparatively high BPV have a relatively high noradrenergic function. This might explain why in our study depressed patients with the highest BPV responded strongest to selective noradrenergic treatment with reboxetine. As measurement of BPV is simple, further studies are suggested to examine the possible clinical value of the link between prolactin, noradrenergic function in major depression and treatment response.
Dysregulated Innate Immune Responses in Young Children with Autism Spectrum Disorders: Their Relationship to Gastrointestinal Symptoms and Dietary Intervention
Authors: Jyonouchi Harumi , Geng Lee , Ruby Agnes , Zimmerman-Bier Barbie
Published: March 2005

Objective: Our previous study indicated an association between cellular immune reactivity to common dietary proteins (DPs) and excessive proinflammatory cytokine production with endotoxin (lipopolysaccharide, LPS), a major stimulant of innate immunity in the gut mucosa, in a subset of autism spectrum disorder (ASD) children. However, it is unclear whether such abnormal LPS responses are intrinsic in these ASD children or the results of chronic gastrointestinal (GI) inflammation secondary to immune reactivity to DPs. This study further explored possible dysregulated production of proinflammatory and counter-regulatory cytokines with LPS in ASD children and its relationship to GI symptoms and the effects of dietary intervention measures. Methods: This study includes ASD children (median age 4.8 years) on the unrestricted (n = 100) or elimination (n = 77) diet appropriate with their immune reactivity. Controls include children with non-allergic food hypersensitivity (NFH; median age 2.9 years) on the unrestricted (n = 14) or elimination (n = 16) diet, and typically developing children (median age 4.5 years, n = 13). The innate immune responses were assessed by measuring production of proinflammatory (TNF-α, IL-1β, IL-6, and IL-12) and counter-regulatory (IL-1ra, IL-10, and sTNFRII) cytokines by peripheral blood mononuclear cells (PBMCs) with LPS. The results were also compared to T-cell responses with common DPs and control T-cell mitogens assessed by measuring T-cell cytokine production. Results: ASD and NFH PBMCs produced higher levels of TNF-α with LPS than controls regardless of dietary interventions. However, only in PBMCs from ASD children with positive gastrointestinal (GI(+)) symptoms, did we find a positive association between TNF-α levels produced with LPS and those with cow’s milk protein (CMP) and its major components regardless of dietary interventions. In the unrestricted diet group, GI(+) ASD PBMCs produced higher IL-12 than controls and less IL-10 than GI(–) ASD PBMCs with LPS. GI(+) ASD but not GI(–) ASD or NFH PBMCs produced less counter-regulatory cytokines with LPS in the unrestricted diet group than in the elimination diet group. There was no significant difference among the study groups with regard to cytokine production in responses to T-cell mitogens and other recall antigens. Conclusion: Our results revealed that there are findings limited to GI(+) ASD PBMCs in both the unrestricted and elimination diet groups. Thus our findings indicate intrinsic defects of innate immune responses in GI(+) ASD children but not in NFH or GI(–) ASD children, suggesting a possible link between GI and behavioral symptoms mediated by innate immune abnormalities.