bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for increased ovarian follicular activity in girls with premature thelarche
Authors: Crofton Patricia M. , Evans Nancy E. M. , Wardhaugh Barbara , Groome Nigel P. , Kelnar Christopher J. H.
Published: January 2005

Objective  Inhibin B is produced by granulosa cells in small antral follicles, under the influence of FSH, and has a paracrine role in oestradiol synthesis. To test the hypothesis that premature thelarche is associated with increased FSH‐driven follicular development, we measured inhibin B and FSH in girls with premature thelarche, girls with central precocious puberty (CPP) and controls matched either for age or breast stage.

Patients  Blood samples were collected from 11 girls with premature thelarche (breast stage 2, aged 0·4–5·6 years), 11 prepubertal controls age‐matched to the thelarche girls (0·5–5·4 years), 13 girls with CPP (breast stage 2, 3·9–8·2 years) and nine normal pubertal controls (breast stage 2, 9·0–13·2 years).

Measurements  Dimeric inhibin B was measured in plasma by double‐antibody enzyme‐linked immunoassay and FSH by immunoradiometric assay. Pelvic ultrasonography was performed on all girls with CPP and 10/11 girls with premature thelarche.

Results  Seven of the 13 girls with CPP and three of the eight girls with premature thelarche whose ovaries could be visualized had visibly nonhomogeneous ovarian structure on ultrasonography. Girls with premature thelarche had inhibin B and FSH concentrations higher than those in their age‐matched controls (P < 0·01 and P < 0·05, respectively), and similar to those observed in girls with CPP and normal pubertal controls matched for breast stage. In thelarche girls, as in precocious puberty girls and normal pubertal controls, inhibin B and FSH were positively related (rs = 0·54–0·61).

Conclusions  This study provides further evidence that premature thelarche is associated with enhanced follicular development, similar to that which occurs in early puberty, probably under the influence of FSH.
The long‐term efficacy of conventional radiotherapy in patients with GH‐secreting pituitary adenomas
Authors: Minniti Giuseppe , Jaffrain‐Rea Marie‐Lise , Osti Mattia , Esposito Vincenzo , Santoro Antonio , Solda Francesca , Gargiulo Patrizia , Tamburrano Guido , Enrici Riccardo Maurizi
Published: January 2005

Objective  To assess the long‐term efficacy and safety of conventional radiotherapy (RT) in the control of acromegaly according to recent stringent criteria of cure.

Design  A retrospective longitudinal study.

Patients and Methods  Forty‐seven patients with active acromegaly were treated with conventional RT between 1982 and 1994. All patients were first operated on and successively irradiated at a dose of 45–50 Gy in 25–28 fractions for persistent (n = 40) or recurrent (n = 7) disease.

Measurements  Long‐term GH/IGF‐I secretion and local tumour control were evaluated regularly, and possible side‐effects were searched for systematically, especially in terms of secondary endocrine dysfunction. Biochemical cure of acromegaly was defined by glucose‐suppressed plasma GH levels below 1 µg/l during an oral glucose tolerance test (OGTT) and normal age‐corrected IGF‐I values.

Results  The 5‐, 10‐ and 15‐year overall survival rates were 98%, 95% and 93%, respectively. Suppression of GH during OGTT was seen in 9% of patients at 2 years, 29% at 5 years, 52% at 10 years, and 77% at 15 years. Age‐corrected IGF‐I levels were normal in 8% of patients 2 years after RT, and this proportion increased to 23%, 42% and 61% after 5, 10 and 15 years, respectively. Normalization of GH/IGF‐I mainly depended on pre‐RT levels. Local tumour control was 95% at 5, 10 and 15 years after treatment. Late toxicity was mainly represented by progressive hypopituitarism, which was present in 33% of patients at baseline and increased to 57%, 78% and in 85% of patients at 5 10 and 15 years after RT, respectively.

Conclusion  Conventional RT is effective in the long‐term control of GH‐secreting pituitary adenomas, although with a high prevalence of progressive hypopituitarism. At present, it remains a suitable option in acromegalic patients uncontrolled by surgery or medical therapy.
Metastasis to the thyroid diagnosed by fine‐needle aspiration biopsy
Authors: Kim Tae Yong , Kim Won Bae , Gong Gyungyub , Hong Suck Joon , Shong Young Kee
Published: January 2005

Background  Metastasis to the thyroid is uncommon, but the number of cases seems to have increased in recent years. This increase may be related to more frequent use of fine‐needle aspiration biopsy (FNAB) in any suspected case.

Design  A retrospective review of patients with thyroid metastasis diagnosed by FNAB at the Asan Medical Centre.

Patients  Twenty‐two patients who were seen at the Asan Medical Centre between 1997 and 2003. Median age was 55 years with range between 34 and 74 years.

Results  Fourteen patients presented with a palpable thyroid nodule. Eight patients had an impalpable thyroid nodule that was found incidentally during the various imaging studies. The breast (five patients) was the most common primary site followed by the kidney (three), colon (three) and lung (three). FNAB confirmed metastatic disease in 19 patients and raised suspicion in three patients. The suspicion of metastasis to the thyroid was confirmed by Tru‐cut needle core biopsy in one patient and surgery in two patients. Thyroid metastases were found during the initial work‐up for primary tumour in eight patients. In the remaining 14 patients, the interval from diagnosis of primary tumour to the detection of thyroid metastasis varied from 8 months to 15 years, with a median of 54 months. Fifteen patients had metastatic disease elsewhere at the time of presentation. Ten patients received chemotherapy. Radiotherapy was used in two patients. Seven patients are still alive, with one patient disease free for 16 months following resection of the thyroid metastasis.

Conclusions  Thyroid metastases are uncommon but can be detected more frequently with routine use of FNAB. Breast cancer is the most common tumour that metastasizes to the thyroid. They usually occur when there are metastases elsewhere, sometimes many years after the diagnosis of the original primary tumour and show poor prognosis in general.
Changes in thyroid hormone state in children receiving chemotherapy
Authors: Van Santen H. M. , Thonissen N. M. , De Kraker J. , Vulsma T.
Published: January 2005

Objective  The concentrations of thyroid function determinants may change during severe illness. Our goal was to quantify their changes in children with cancer during chemotherapy, and to correlate them to clinical condition and type of drugs.

Design  During a 3‐month period all patients admitted for chemotherapy to the paediatric oncology ward were evaluated for inclusion. Patients with brain tumours, neuroblastoma (cranio)spinal irradiation and use of dexamethasone before the first blood sample were excluded.

Measurements  Plasma concentrations of T4, T3, rT3, thyroxine‐binding globulin (TBG), thyroglobulin (Tg), TSH, IGF‐1, cortisol, PRL and physical well‐being by means of questionnaires were measured before and during chemotherapy.

Results  In 19 children, 46 courses of chemotherapy and 123 plasma samples were analysed. During chemotherapy, mean concentrations of TSH, T3, Tg and cortisol decreased to 53, 67, 69 and 15% of the baseline value, respectively. Mean plasma rT3 increased to 217% of baseline. In 87% of all courses, one or more thyroid parameter(s) was aberrant. Furthermore, in 23 samples (19%) from 10 patients (53%), the concentration of IGF‐1 was below the reference value (adjusted for sex and age). Small changes were seen in scores for clinical condition but none was related to a change in thyroid function determinant. Most changes in thyroid hormones could be attributed to using dexamethasone.

Conclusions  These results demonstrate that, in children, thyroid hormone state changes significantly during chemotherapy, apparently not related to physical well‐being but to the drugs administered. Future investigations should focus on the impact for patient care and possibilities of (preventive) intervention.
Is stimulation of thyroglobulin (Tg) useful in low‐risk patients with thyroid carcinoma and undetectable Tg on thyroxin and negative neck ultrasound?
Authors: Do Rosário Pedro Weslley Souza , Borges Michelle Aparecida Ribeiro , Fagundes Tales Alvarenga , Franco Ana Cristina Horta Messias , Purisch Saulo
Published: January 2005

Objective  To determine the usefulness of thyroglobulin (Tg) stimulation in low‐risk patients with undetectable Tg on T4 and negative neck ultrasound (US) after initial therapy of thyroid carcinoma.

Methods  We evaluated 122 consecutive patients classified as low risk 6 months to 1 year after total thyroidectomy and remnant ablation. All patients had a normal clinical exam, Tg ≤ 1 ng/ml during suppressive therapy (TSH < 0·1 mIU/l), and undetectable antithyroglobulin antibodies.

Results  After T4 withdrawal and elevation of TSH to values > 30 mIU/l, 26 patients (21·3%) converted Tg to levels > 1 ng/ml. Metastases were detected in 10 patients, nine showing stimulated Tg levels > 1 ng/ml. Cervical metastases were observed in 9/10 patients and lung metastases in one patient. Neck US identified all cervical metastases. Seventeen patients with stimulated Tg levels > 1 ng/ml initially showed no apparent disease, with a reduction in Tg being observed upon subsequent measurements, and 13 patients presented undetectable Tg off T4 at the end of the study. Undetectable Tg on T4 showed a high negative predictive value (NPV; 91·8%), which increased to 99·1% when combined with neck US. Stimulated Tg levels < 1 ng/ml presented a 98·9% NPV. A total of 113 patients with undetectable Tg on T4 and negative US had to be exposed to hypothyroidism in order to diagnose one further case of metastases.

Conclusion  Undetectable Tg on T4 combined with negative neck US presented a high NPV in low‐risk patients and Tg stimulation might be avoided in these patients.
Intrinsic nuclear import activity of geminin is essential to prevent re‐initiation of DNA replication in Xenopus eggs
Authors: Yoshida Kazumasa , Takisawa Haruhiko , Kubota Yumiko
Published: January 2005

Prior to S phase, eukaryotic chromosomes are licensed for initiation of DNA replication, and re‐licensing is prohibited after S phase has started until late mitosis, thus ensuring that genomic DNA is duplicated precisely once in each cell cycle. Here, we report that over‐expression of Cdt1, an essential licensing protein, induced re‐replication in Xenopus egg extracts. Geminin, a metazoan‐specific inhibitor of Cdt1, was critical for preventing re‐replication induced by Cdt1. Re‐replication induced by the addition of recombinant Cdt1 and/or by the depletion of geminin from extracts was enhanced by a proteasome inhibitor, which suppressed the degradation of Cdt1 in the extracts. Furthermore, a nuclear localization sequence identified in Xenopus geminin had a significant role in the suppression of re‐replication induced by Cdt1. These results suggest that nuclear accumulation of geminin plays a dominant role in the licensing system of Xenopus eggs.
Centrosome‐targeting region of CG‐NAP causes centrosome amplification by recruiting cyclin E‐cdk2 complex
Authors: Nishimura Tamako , Takahashi Mikiko , Kim Hon‐Song , Mukai Hideyuki , Ono Yoshitaka
Published: January 2005

Centrosome duplication occurs once per cell cycle and is thought to be triggered by cyclin E‐cdk2. However, it is largely unknown how the duplication is regulated. Here, we found that the expression of the centrosome‐targeting region of CG‐NAP (centrosome and Golgi‐localized PKN‐associated protein), which we designate as CG‐NAP/D, increased the number of centrosomes in Chinese hamster ovary (CHO)‐K1 cells. The amplified centrosomes co‐localized with centrosome markers γ‐tubulin, centrin‐2 and kendrin as well as endogenous CG‐NAP. When CG‐NAP/D was dislocated from centrosomes by deleting the centrosome‐targeting domain or by fusing with a membrane‐targeting sequence, centrosome amplification was suppressed. CG‐NAP/D interacted with exogenously expressed cyclin E, which co‐localized at centrosomes. The immunoprecipitates of CG‐NAP/D exhibited histone H1 kinase activity, suggesting the co‐immunoprecipitation of active cyclin‐cdk complexes. Furthermore, centrosome fractions prepared from cells expressing CG‐NAP/D contained increased amount of cdk2 compared with those from control cells. Centrosome amplification by CG‐NAP/D was suppressed by co‐expression of a mutant cyclin E unable to interact with cdk2. These results suggest that CG‐NAP/D causes centrosome amplification by anchoring excess amount of cyclin E‐cdk2 to centrosomes and, possibly, CG‐NAP participates in centrosome duplication by recruiting cyclin E‐cdk2 to centrosomes in normal cell cycle.
LIGHT is involved in the pathogenesis of rheumatoid arthritis by inducing the expression of pro‐inflammatory cytokines and MMP‐9 in macrophages
Authors: Kim Won‐Jung , Kang Yoon‐Joong , Koh Eun‐Mi , Ahn Kwang‐Sung , Cha Hoon‐Suk , Lee Won‐Ha
Published: January 2005

Macrophages play a crucial role in the perpetuation of inflammation and irreversible cartilage damage during the development of rheumatoid arthritis (RA). LIGHT (TNFSF14) and its receptor TR2 (TNFRSF14) are known to have pro‐inflammatory activities in foam cells of atherosclerotic plaques. We tested a hypothesis that LIGHT and TR2 are involved in activation of monocyte/macrophages in RA synovium. Immunohistochemical analysis of RA synovial tissue samples revealed that both LIGHT and TR2 are expressed in CD68 positive macrophages. In contrast, synovial tissue samples from osteoarthritis (OA) patients failed to reveal the expression of LIGHT. Expression of TR2 in RA synovial macrophages was also detected using flow cytometry analysis. To identify the role of LIGHT in the functioning of macrophages in RA, we isolated macrophage enriched cells from RA synovial fluid and stimulated them with LIGHT. LIGHT induced expression of matrix metalloproteinase‐9 and pro‐inflammatory cytokines such as tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, and IL‐8. These data indicate that LIGHT and TR2 expressed in macrophages are involved in the pathogenesis of RA by inducing the expression pro‐inflammatory cytokines and matrix degrading enzymes.
Significance of Fas and Fas ligand in tuberculous lymphadenitis
Authors: Mustafa Tehmina , Mogga Stanley J. , Mfinanga Sayoki G. M. , Mørkve Odd , Sviland Lisbet
Published: January 2005

The Fas/Fas‐ligand (FasL) system plays an important role in regulation of apoptosis and the immune response, and is exploited by mycobacteria to evade the immune response. This study was performed to investigate the distribution and levels of FasL and Fas in lymph node granulomas and sera of tuberculous lymphadenitis patients by immunohistochemistry and enzyme‐linked immunosorbent assay. The validity of soluble Fas (sFas) or soluble FasL (sFasL) as a diagnostic tool was also examined. Levels of sFasL in serum were elevated among patients. The numbers of FasL stained cells in lymph node granulomas were higher than Fas. Children had significantly higher levels of sFasL as compared to adults. The human immunodeficiency virus (HIV)–tuberculosis (TB)‐coinfected patients displayed no differences in the levels of sFasL or sFas compared with HIV‐negative patients. The healthy controls from a high endemic tuberculosis country (having latent TB) had significantly higher levels of sFasL than from a country with no TB transmission. The sensitivity and specificity of the FasL and Fas test were low when compared with the culture results as the gold standard. However, by using histology as the gold standard, the sensitivity and specificity of the FasL test were increased to 66·7% and 100%, respectively, but for the Fas test remained low. In conclusion, sFasL and sFas cannot be used as diagnostic tests for tuberculous lymphadenitis. However, its utility in detecting latent TB and childhood tuberculous lymphadenitis remains to be evaluated. FasL seems to play a role in immune modulation and pathogenesis of TB. Modulators of Fas/FasL‐mediated apoptosis may therefore be clinically useful.
VH replacement in rearranged immunoglobulin genes
Authors: Darlow John M. , Stott David I.
Published: January 2005

Examples suggesting that all or part of the VH segment of a rearranged VHDJH may be replaced by all or part of another VH have been appearing since the 1980s. Evidence has been presented of two rather different types of replacement. One of these has gained acceptance and has now been clearly demonstrated to occur. The other, proposed more recently, has not yet gained general acceptance because the same effect can be produced by polymerase chain reaction artefact. We review both types of replacement including a critical examination of evidence for the latter. The first type involves RAG proteins and recombination signal sequences (RSS) and occurs in immature B cells. The second was also thought to be brought about by RAG proteins and RSS. However, it has been reported in hypermutating cells which are not thought to express RAG proteins but in which activation‐induced cytidine deaminase (AID) has recently been shown to initiate homologous recombination. Re‐examination of the published sequences reveals AID target sites in VH‐VH junction regions and examples that resemble gene conversion.
Intranasal inoculation of Chlamydia trachomatis mouse pneumonitis agent induces significant neutrophil infiltration which is not efficient in controlling the infection in mice
Authors: Bai Hong , Yang Jie , Qiu Hongyu , Wang Shuhe , Fan Yijun , Han Xiaobing , Xie Shusheng , Yang Xi
Published: January 2005

Previous studies have shown that chlamydial infection is accompanied by significant infiltration of neutrophils at the site of infection. However, the role of neutrophils in host defence against chlamydial infection is not clearly understood. Using genetically different inbred mouse strains and CXCR‐2 gene knockout (KO) mice, we examined the mechanism for neutrophil recruitment and the role of neutrophils during chlamydial lung infection. Our data showed that C3H mice exhibited significantly higher and more persistent neutrophil infiltration in the lung than did C57BL/6 mice following Chlamydia trachomatis mouse pneumonitis infection. The massive neutrophil infiltration in C3H mice was paralleled by high‐level expression of CXCR‐2 and its ligands, CXC chemokines (macrophage inflammatory protein 2, cytokine‐induced neutrophil attractant (KC) and lipopolysaccharide‐induced CXC chemokine), and proinflammatory cytokines (tumour necrosis factor‐α, interleukin‐1 and interleukin‐6) in the lung. Although much greater infiltration of neutrophils was observed in C3H mice than in C57BL/6 mice, the former mice had more severe disease and higher in vivo chlamydial growth than the latter. Moreover, CXCR‐2 KO mice, which revealed a dramatic reduction in neutrophil activity, showed comparable chlamydial infection to wild‐type mice. These results suggest that neutrophils are not efficient for controlling chlamydial lung infection.
Antibody repertoire development in fetal and neonatal piglets. XI. The thymic B‐cell repertoire develops independently from that in blood and mesenteric lymph nodes
Authors: McAleer Jeremy , Weber Patrick , Sun Jishan , Butler John E.
Published: January 2005

The origin and function of thymic B cells is currently unresolved. In the present study we compared VH gene repertoire diversification in >3500 cloned VDJs (from 11 animals at three time‐points, using three to five animals per time‐point) that were expressed with immunoglobulin (Ig)M, IgD, IgG, IgA and IgE in thymus, mesenteric lymph nodes (MLN) and peripheral blood B cells (PBB) of newborn piglets and 5‐week‐old isolator piglets maintained germfree (GF) or colonized with Escherichia coli. The results showed that the repertoire expressed with IgM, IgD, IgG and IgA in PBB and MLN remained polyclonal, undiversified and unselected in piglets maintained GF for 5 weeks, that age and colonization resulted in significant repertoire diversification of IgG and IgA in the MLN and of IgG in blood, that the thymic B‐cell repertoire was polyclonal, unaffected by colonization and showed no clonal selection in any isotype, and that the thymic IgA and IgE repertoires were more diverse at birth than the repertoire of any isotype in MLN or PBB. IgD was seldom recovered from the PBB of newborn piglets or at any time‐point in thymus, but was recovered in the MLN of all 11 animals examined. The IgD and IgM repertoires in all tissues remained polyclonal and unselected, although VH usage by IgD transcripts did not always parallel that of IgM in the same tissue. Therefore, isotype‐switched B cells in the thymic medulla cannot be accounted for by immigration of B cells diversified by colonization of the gut, and thymic B cells undergo switch recombination and repertoire diversification before birth without clonal selection.
Aberrant regulation of interleukin‐12 receptor β2 chain on type 1 cytokine‐stimulated T lymphocytes in type 1 diabetes
Authors: Skarsvik Susanne , Ludvigsson Johnny , Vaarala Outi
Published: January 2005

An aberrant mitogen‐induced polarization of peripheral blood T cells has been associated with type 1 diabetes (T1D). We studied, in T1D, type 1 and 2 cytokine‐induced expression of the interleukin‐12 receptor β2 chain (IL‐12Rβ2 chain), which plays a critical role in regulating T‐cell polarization. Peripheral blood lymphocytes from children with newly diagnosed T1D (n = 10; mean age 10 years), from children with longstanding T1D (n = 8; mean age 12·9 years) and from healthy children (n = 15; mean age 11·5 years) were stimulated with phytohaemagglutinin (PHA) in a type 1 (IL‐12 and anti‐IL‐4) or a type 2 (IL‐4 and anti‐IL‐12) cytokine environment. Secretion of interferon‐γ (IFN‐γ), IL‐5 and IL‐13, as detected by enzyme‐linked immunosorbent assay (ELISA), and expression of the IL‐12Rβ2 chain on CD4 and CD8 cells by flow cytometry, were analysed. Children with newly diagnosed and longstanding T1D had lower expression levels of the IL‐12Rβ2 chain on IL‐12Rβ2 chain‐positive CD4 T cells (for a type 1 or a type 2 cytokine environment: P = 0·01 and P = 0·002 or P = 0·02 and P = 0·01, respectively) and on IL‐12Rβ2 chain‐positive CD8 T cells (for a type 1 or a type 2 cytokine environment: P = 0·007 and P = 0·0007 or P = 0·003 and P = 0·01, respectively) when compared to healthy children. A decreased percentage of IL‐12Rβ2 chain‐expressing CD4 T cells (P = 0·07 and P = 0·03) and CD8 T cells (P = 0·004 and P = 0·01) and increased secretion of IL‐13 (P = 0·006 and P = 0·04) in a type 1 cytokine environment was seen in both groups of patients. Peripheral blood T cells from patients with both newly diagnosed and longstanding T1D showed poor polarization towards type 1 cells.
Overlap of gastrointestional symptom complexes in a US community
Authors: Locke G. R. , Zinsmeister A. R. , Fett S. L. , Melton L. J. , Talley N. J.
Published: January 2005

Abstract  Background:  Although the Rome criteria define a number of individual functional gastrointestinal disorders, people may have symptoms of multiple disorders at the same time. In addition, therapies may be effective in subsets of people with specific disorders, yet at the same time help people with multiple disorders.

Aim:  To estimate the prevalence of combinations of gastrointestional (GI) symptom complexes.

Methods:  A valid self report questionnaire which records GI symptoms was mailed to an age‐ and gender‐stratified random sample of Olmsted County, MN residents aged 30–64 years. Standard definitions were used to identify people with gastro‐oesophageal reflux, dyspepsia, irritable bowel syndrome (IBS), constipation and diarrhoea. The prevalence of people meeting multiple symptom complexes was estimated. Specifically, combinations of dyspepsia, IBS and constipation were compared to dyspepsia, IBS and diarrhoea.

Results:  A total of 657 (69%) of 943 eligible subjects responded; 643 provided data for each of the necessary symptom questions. Each two‐way combination of symptom group was present in between 4 and 9% of the population; each three‐way combination was present in 1–4% of the population. The overlap between dyspepsia, IBS and constipation was similar to dyspepsia, IBS and diarrhoea, except body mass index was higher in the diarrhoea overlap group (P = 0.03).

Conclusion:  Symptom complex overlap is common in the community; for each condition, the majority of sufferers reported an additional symptom complex. This overlap of symptoms challenges the current paradigm that functional GI disorders represent multiple discreet entities.
Vagal selective effects of ruthenium red on the jejunal afferent fibre response to ischaemia in the rat
Authors: Bulmer D. C. E. , Jiang W. , Hicks G. A. , Davis J. B. , Winchester W. J. , Grundy D.
Published: January 2005

Abstract  A variety of inflammatory mediators and local metabolites, have been implicated in the sensitivity of intestinal afferent fibres to brief periods of ischaemia and reperfusion. As yet, the contribution of the vanilloid transient receptor potential (TRPV)1 receptor to the response to intestinal ischaemia remains undetermined. In the present study, the effect of pretreatment with the competitive TRPV1 antagonist capsazepine and the non‐selective TRPV channel antagonist ruthenium red, on the mesenteric afferent fibre response to ischaemia was examined. In control animals there was a reproducible biphasic increase in whole nerve afferent fibre activity during two brief periods of ischaemia. Treatment with ruthenium red significantly attenuated the early phase increase in afferent fibre activity during ischaemia. However, capsazepine treatment did not significantly alter the afferent fibre response to either ischaemia or reperfusion. Further experiments in chronically vagotomized animals indicated that the early phase response to ischaemia was mediated via vagal afferent fibres. The mechanism via which ruthenium red selectively inhibited vagal afferent fibres during ischaemia is unknown, but it does not appear to involve blockade of the TRPV1 receptor.
Magnetic pill tracking: a novel non‐invasive tool for investigation of human digestive motility
Authors: Stathopoulos E. , Schlageter V. , Meyrat B. , de Ribaupierre Y. , Kucera P.
Published: January 2005

Abstract  A new minimally invasive technique allowing for anatomical mapping and motility studies along the entire human digestive system is presented. The technique is based on continuous tracking of a small magnet progressing through the digestive tract. The coordinates of the magnet are calculated from signals recorded by 16 magnetic field sensors located over the abdomen. The magnet position, orientation and trajectory are displayed in real time. Ten young healthy volunteers were followed during 34 h. The technique was well tolerated and no complication was encountered. The information obtained was 3‐D configuration of the digestive tract and dynamics of the magnet displacement (velocity, transit time, length estimation, rhythms). In the same individual, repeated examination gave very reproducible results. The anatomical and physiological information obtained corresponded well to data from current methods and imaging. This simple, minimally invasive technique permits examination of the entire digestive tract and is suitable for both research and clinical studies. In combination with other methods, it may represent a useful tool for studies of GI motility with respect to normal and pathological conditions.
Hypersensitivity to ovalbumin induces chronic intestinal dysmotility and increases the number of intestinal mast cells
Authors: Saavedra Y. , Vergara P.
Published: January 2005

Abstract  Undiagnosed food allergies have been proposed as possible causes of promoting and perpetuating irritable bowel syndrome . Our aim was to find out if sensitization could induce chronic functional motor disturbances in the intestine and the mechanisms implicated. Rats were sensitized to ovalbumin (OVA) following three hypersensitivity induction protocols, two parenteral and one oral. Rat mast cell protease II (RMCP II) release in response to OVA challenge and immunoglobulin E (IgE) concentration were measured in serum. At least 1 week after challenge, small intestinal motility was evaluated using strain gauges. Intestinal tissue samples from orally sensitized rats were checked for in vitro stimulation with OVA. Mucosal mast cells were counted from duodenum sections. All sensitized rats showed intestinal hypermotility. Only rats sensitized by parenteral procedure showed an increase in RMCP II after OVA challenge in serum. IgEs increased only in the Bordetella pertussis sensitized group. Small intestine sections from orally sensitized rats released more RMCP II than sections from control rats. All sensitized rats showed an increase in the number of mucosal mast cells in duodenum. In conclusion, hypersensitivity to food proteins induces chronic motor alteration that persists long after antigen challenge and an excited/activated state of sensitized mucosal mast cells.
Is gastric electrical stimulation superior to standard pharmacologic therapy in improving GI symptoms, healthcare resources, and long‐term health care benefits?
Authors: Cutts T. F. , Luo J. , Starkebaum W. , Rashed H. , Abell T. L.
Published: January 2005

Abstract  Context:  Severe upper gastrointestinal (GI) motor disorders, including gastroparesis (GP), can consume significant health care resources. Many patients are refractory to traditional drug therapy.

Objective:  To compare symptoms, healthcare resource utilization and costs in two groups of patients with the symptoms of GP: those treated via gastric electrical stimulation (GES) and those treated with traditional pharmacological agents in an intensive outpatient program (MED).

Design:  A long‐term comparison of patients with devices (n = 9) vs intensive medical therapy (n = 9).

Setting and patients: A total of 18 eligible patients with the symptoms of GP reported for 1‐year baseline and long‐term treatment for 3 years.

Interventions:  Patients with the symptoms of GP were treated by a GES or intensive medical therapy (MED).

Main outcome measures:  GP Symptoms, healthcare resource utilization using investigator‐derived independent outcome measure score (IDIOMS) and total hospital (inpatient and outpatient) billing costs.

Results:  Gastrointestinal symptoms were significantly different from baseline (F = 3.03, P < 0.017) with GP patients treated via GES showing more sustained improvement over 36 months than those treated via MED. Healthcare resource usage, measured via the IDIOMS, significantly improved at 12, 24 and 36 month follow‐up for GES patients (F = 10.49, P < 0.001), compared with patients receiving medical therapy, who demonstrated further deterioration. GP patients treated via GES also proved superior to medical therapy at 24 and 36 months with regard to decreased costs (F = 4.85, P < 0.001). Within group comparisons indicated significantly reduced hospital days for both patient groups; however, no statistical differences were noted between groups in terms of hospital days. Three of nine patients in the MED group died primarily from i.v. access related problems; none of the GES patients died.

Conclusion:  We conclude that GES is more effective in improving long‐term GI symptoms and costs, and decreasing use of healthcare resources than intensive medical therapy, in this sample of patients with the symptoms of GP followed for 3 years. Certain patients with GP form a high‐risk group in terms of costs, quality of life, morbidity and mortality.
Reproducibility of meal‐induced transient lower oesophageal sphincter relaxations in patients with gastro‐oesophageal reflux disease
Authors: Boeckxstaens G. E. , Hirsch D. P. , Verkleij C. B. , Lei A. , Holman R. , Lehmann A. , Rydholm H.
Published: January 2005

Abstract Aim:  To calculate the number of subjects required in trials investigating drugs reducing the number of transient lower oesophageal sphincter relaxations (TLOSRs), the inter‐ and intra‐individual variability of TLOSRs were determined, using meal ingestion as a trigger of TLOSRs and reflux.

Methods:  A total of 23 gastro‐oesophageal reflux disease (GORD) patients with no to grade B oesophagitis and a hiatal hernia ≤3 cm underwent oesophageal manometry and pHmetry 1 h before and 3 h after ingestion of a solid meal on two separate days approximately 4 weeks apart. Reflux episodes and the underlying mechanisms and the number of TLOSRs were evaluated.

Results:  The number of TLOSRs, reflux episodes and % time with pH < 4 after meal ingestion did not differ significantly between the two sessions. The intra‐individual variation of TLOSRs in the 3 h postprandial period (24.4) was smaller compared with the inter‐individual variation (47.5). Transient lower oesophageal sphincter relaxations were the predominant cause of reflux accounting for 61 ± 7 and 70 ± 5% of the reflux episodes in visits 1 and 2, respectively.

Conclusions:  These data for the first time provide information on the variability of TLOSRs and reflux evoked by meal ingestion, which is of crucial importance for the design and power calculations of future clinical studies evaluating the efficacy of new drugs targeting TLOSRs.
A randomized‐controlled trial comparing an educational intervention alone vs education and biofeedback in the management of faecal incontinence in women
Authors: Ilnyckyj A. , Fachnie E. , Tougas G.
Published: January 2005

Abstract  Biofeedback (BF) training is an accepted therapy in the treatment of faecal incontinence (FI) despite a paucity of data demonstrating benefit. This study aims to determine whether BF has any specific effect above and beyond an educational intervention. Twenty‐three women with regular and frequent idiopathic FI were randomized to education and pelvic exercise vs education and BF therapy. Complete data is available for 18 women. Overall, 61% of participants demonstrated a complete response. There was no difference in response rate between treatment arms. Women with FI demonstrate a good response to treatment with education and exercise and education plus BF thus questioning the specific effect of BF.
Ileal myenteric plexus in aged guinea‐pigs: loss of structure and calretinin‐immunoreactive neurones
Authors: Abalo Raquel , José rivera Antorio , Vera Gema , Isabel Martín M.
Published: January 2005

Abstract  Myenteric plexus controls gastrointestinal motility by means of well organized circuits which are comprised of sensory neurones, interneurones and motor neurones to the muscular layers. Calretinin (CR) is a calcium‐binding protein that, in guinea‐pig ileum, has only been found in ascending interneurones, which also express neurofilament triplet proteins (NFT), and excitatory longitudinal muscle motor neurones, which do not. In spite of some evidence that age affects both function and structure of the myenteric plexus, little is known about the possible selectivity of the process regarding specific myenteric neuronal phenotypes. The influence of age on both the structure of the myenteric plexus and the presence of CR‐immunoreactive (CR‐IR) neurones was studied using conventional immunohistochemical procedures applied to ileal whole‐mount preparations from guinea‐pigs. Both a reduction in ganglionic size and changes in the distribution of neurones inside and outside the ganglia, together with a general neuronal loss were found in preparations from aged guinea‐pigs. More interestingly, a relatively more pronounced age‐related loss of CR‐IR neurones, especially those lacking of NFT expression, was found. Specific myenteric neuronal phenotypes may show differential sensitivity to ageing, and this could, under certain circumstances, alter the functional balance of gastrointestinal motility in aged individuals.
Accumulation and localization of aluminium in root tips of loblolly pine seedlings and the associated ectomycorrhiza Pisolithus tinctorius
Authors: MOYER‐HENRY K. , SILVA I. , MACFALL J. , JOHANNES E. , ALLEN N. , GOLDFARB B. , RUFTY T.
Published: January 2005

Evidence from past studies suggests that loblolly pine may be tolerant of Al. The experiments described in this manuscript were initiated to examine Al tolerance and Al accumulation in the pine root and the degree of Al accumulation in fungal hyphae when pine roots were colonized with the ectomycorrhiza Pisolithus tinctorius. The experiments used lumogallion staining and confocal microscopy to localize Al in root and fungal structures. The results clearly showed that loblolly pine seedlings were highly resistant to Al. A decrease in primary root extension could not be detected until Al+3 activities approached 40 µmol L−1, and extension was suppressed only 30% at an Al+3 activity of 580 µmol L−1. This contrasted with the response of the Al‐sensitive ‘check’ species soybean, where primary root extension was severely restricted at Al+3 activities lower than 5 µmol L−1. Tissue Al measurements and lumogallion fluorescence of longitudinal sections of the pine root tip indicated that tolerance was associated with both Al exclusion from the tip region and compartmentalization of absorbed Al in peripheral cell areas outside of the meristem. In lateral roots colonized with ectomycorrhizae, lumogallion fluorescence showed that large amounts of Al accumulated at the fungal mantle and in areas with the Hartig net. At higher magnification, lumogallion indicated substantial Al accumulation inside hyphae. Little Al could be detected in lateral root cells. The results show that pine possesses multiple mechanisms that can contribute to Al tolerance in acid field soils.
Blockage of apoplastic bypass‐flow of water in rice roots by insoluble salt precipitates analogous to a Pfeffer cell
Authors: RANATHUNGE K. , STEUDLE E. , LAFITTE R.
Published: January 2005

Precipitates of insoluble inorganic salts were used to clog apoplastic pores in cell walls of the outer part of rice roots (OPR) in two rice cultivars (lowland cv. IR64 and upland cv. Azucena). Aerenchyma of two different root zones (20–50 and 50–100 mm from the apex) was perfused with 1 m m potassium ferrocyanide (K4[Fe(CN)6]) while the whole root segments were bathed in 0.5 m m copper sulphate (CuSO4) medium. In another experiment, salts were applied on opposite sides of the OPR. The copper‐ferrocyanide precipitation technique resembles the famous osmotic experiments of the German botanist Wilhelm Pfeffer, in which he used them with clay diaphragms. Precipitates were observed on the side where ferrocyanide was applied, suggesting that Cu2+ and SO42– were passing the barrier including the Casparian bands of the exodermis much faster than ferrocyanide. There was a patchiness in the formation of precipitates, correlated with the maturation of the exodermis. The intensity of copper ferrocyanide staining decreased along developing rice roots. No precipitates were observed in mature parts beyond 70–80 mm from the root apex, except for sites around the emergence of secondary roots, which were fairly leaky to both water and ions. Blockage of the apoplastic pores with precipitates caused a three‐ to four‐fold reduction of hydraulic conductivity of the OPR (LpOPR). The reflection coefficient of the OPR (σsOPR) increased in response to the blockage with precipitates. The osmotic versus diffusive water permeability ratios of the OPR (PfOPR/PdOPR) were around 600 for immature and 1200 for mature root segments. Treatment significantly affected the bulk rather than the diffusive water flow and caused a three‐ to five‐fold reduction of the PfOPR/PdOPR ratios. Results indicated that despite the existence of an exodermis with Casparian bands, most of the water moved around cells rather than using the cell‐to‐cell passage.
Transverse hydraulic redistribution by a grapevine
Authors: SMART D. R. , CARLISLE E. , GOEBEL M. , NÚÑEZ B. A.
Published: January 2005

Root hydraulic redistribution has been shown to occur in numerous plant species under both field and laboratory conditions. To date, such water redistribution has been demonstrated in two fundamental ways, either lifting water from deep edaphic sources to dry surface soils or redistributing water downward (reverse flow) when inverted soil Ψs gradients exist. The importance of hydraulic redistribution is not well documented in agricultural ecosystems under field conditions, and would be important because water availability can be temporally and spatially constrained. Herein we report that a North American grapevine hybrid (Vitis riparia × V. berlandieri cv 420 A) growing in an agricultural ecosystem can redistribute water from a restricted zone of available water under a drip irrigation emitter, laterally across the high resistance pathways of the trunk and into roots and soils on the non‐irrigated side. Deuterium‐labelled water was used to demonstrate lateral movement across the vine's trunk and reverse flow into roots. Water redistribution from the zone of available water and into roots distant from the source occurred within a relatively short time frame of 36 h, although overnight deposition into rhizosphere soils around the roots was not detected. Deuterium was eventually detected in rhizosphere soils adjacent to roots on the non‐irrigated side after 7 d. Application of identical amounts of water with the same deuterium enrichment level (2%) to soils without grapevine roots showed that physical transport of water through the vapour phase could not account for either downward or transverse movement of the label. These results confirmed that root presence facilitated the transport of label into soils distant from the wetted zone. When deuterium‐labelled water was allowed to flow directly into the trunk above the root–trunk interface, reverse flow occurred and lateral movement across the trunk and into roots originating around the collar region did not encounter large disproportionate resistances. Rapid redistribution of water into the entire root system may have important implications for woody perennial cultivars growing where water availability is spatially heterogeneous. Under the predominantly dry soil conditions studied in this investigation, water redistributed into roots may extend root longevity and increase the vines water capacitance during periods of high transpiration demand. These benefits would be enhanced by diminished water loss from roots, and could be equally important to other cited benefits of hydraulic redistribution into soils such as enhancement of nutrient acquisition.
Influence of anoxia on whole plant sulphur nutrition of flooding‐tolerant poplar (Populus tremula × P. alba)
Authors: HERSCHBACH C. , MULT S. , KREUZWIESER J. , KOPRIVA S.
Published: January 2005

The investigations reported herein were performed to test whether anoxic soil conditions changed the sink strength of the roots for reduced sulphur and therefore transport of sulphur in the phloem, and whether increasing sulphide contents in anoxic soils due to bacteria activity causes changes in sulphate assimilation of the roots. Anoxic conditions caused by flooding of the flooding‐tolerant tree species Populus tremula × P. alba led not only to changes in carbon metabolism, but also influenced sulphate assimilation. In the roots, activity and transcript of adenosine 5′‐phosphosulphate (APS) reductase, the key enzyme of the sulphate assimilation pathway, completely disappeared, but the Cys content increased 6.7 times after 15 d of flooding. A higher glutathione content of phloem exudates after 3 and 7 d of flooding indicates an increased transport of reduced sulphur to the roots. However, the export rate of 35S‐sulphur out of mature leaves after flap feeding 35S‐sulphate was not different between flooded and control poplars. Since the allocation to the roots was diminished, enhanced phloem contents of GSH indicate a diminished sink strength of the roots rather than an enhanced sink strength. Therefore, a higher transport of GSH in the phloem could not be responsible for the higher Cys content in the roots. As protein contents were unaffected the higher Cys content in roots could also not originate from protein breakdown. Enhanced O‐acetylserine (thiol) lyase (OASTL) activity were measured in the roots demonstrating an uncoupling of sulphate reduction and Cys synthesis. A possible contribution in detoxification of sulphide produced in the anoxic soil is discussed.
Growth responses and fitness costs after induction of pathogen resistance depend on environmental conditions
Authors: DIETRICH R. , PLOSS K. , HEIL M.
Published: January 2005

Fitness costs of resistance are among the most widely discussed explanations for the evolution of induced resistance, but studies on induced resistance to pathogens are scarce and contradictory. In the present study the influence of nitrogen supply, length of the growing period and competition on the seed production of Arabidopsis in response to treatment with the chemical resistance elicitor BION® was investigated. BION® treatment elicited resistance to the bacterial pathogen Pseudomonas syringae, and biochemical changes after BION® treatment were similar to those observed after bacterial infection. Induced plants grew more slowly during the first week after resistance induction, for which they then compensated by exhibiting faster growth than controls. Whether or not induced plants produced less seeds than controls depended on growing conditions. Costs, no costs and even higher seed production by induced plants were observed in experiments differently combining abiotic conditions. A higher seed production by induced plants arose particularly when the vegetation period was short, most probably a consequence of senescence‐related processes that had been activated by resistance elicitation. Induced plants, however, produced less seeds when competing with controls and experiencing a full growing period. Studies controlling only some of the critical environmental factors can easily lead to apparently contradictory results, which in fact represent different outcomes of a complex interplay of factors.
Natural variation in the regulation of leaf senescence and relation to other traits in Arabidopsis
Authors: LEVEY S. , WINGLER A.
Published: January 2005

Leaf senescence results in the recycling of nutrients, thereby providing resources required for growth and reproduction. In this study, the effect of day‐length on leaf senescence in eight different Arabidopsis thaliana ecotypes was determined and the relationship between senescence and other morphological and life history traits was analysed. A significant variation in the start and extent of leaf senescence depending on the genetic background and the response to day‐length was found. Whereas senescence of early flowering ecotypes was accelerated by long days, no effect of day‐length on senescence could be found in late flowering Kas‐1 plants. Senescence in the different ecotypes was associated with other traits, such as floral transition, the total number of fruits, the total number of leaves and the maximum chlorophyll content. Plants that bolted early also senesced early, produced fewer leaves, accumulated less chlorophyll, but produced more fruits. The present results indicate that senescence may be a key component in the trade‐off between investment in photosynthetic capacity and reproduction. The relationship between senescence and other traits was maintained independent of whether differences in senescence were caused by genetic (ecotype) or environmental (day‐length) variation, suggesting that genetic and environmental factors affect these traits through common regulatory pathways.